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Leaders and scholars from multiple academies of the American Physical Therapy Association are developing and defining movement system diagnoses to guide practice. However, there is no consensus on the need for or content of such frameworks. This Perspective describes current thought about movement system diagnoses in physical therapy and summarizes the work of the Academy of Geriatrics (APTA Geriatrics) Movement System Diagnosis Task Force (GMS-TF) as it contributes to the movement system diagnosis discussion within the profession. Initially convened to define movement system diagnostic labels unique to older adults, the GMS-TF's developmental process identified the need for a clearer diagnostic framework onto which specific diagnoses will later be added. Although The World Health Organization International Classification of Functioning, Disability and Health model is a strong foundation for the patient-client management model, the GMS-TF proposes formal incorporation of the Geriatric 5Ms (mobility, medications, memory, multi-complexity, and "what matters most") into a movement system framework for older adults. The GMS-TF concurs with the APTA Academy of Neurology Movement System Task Force proposal that observation and analysis of key functional tasks are the foundation of any examination of older adults. The GMS-TF suggests adding several additional movement tasks that are important for older adults. The GMS-TF believes that this strategy highlights the health care needs of older adults and prioritizes physical therapist care for older adults with complex needs. This Perspective is the foundation for a future movement system diagnosis model for older adults that will complement and facilitate the development of models of care to be applied across the lifespan., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The aim of this study was to investigate whether a 6-week Divided-Attention Stepping Accuracy Task (DATSAT) intervention improved the primary outcome measure, maximal step length; other balance measures (Berg Balance scale and Timed Up and Go test); leg strength; endurance (6-min walk test); and functional tasks in 15 community-dwelling healthy older adults ( x ¯ age: 71.5 years, female: 46.7%) compared with 15 community-dwelling healthy older adults in a Bike and Strength (B&S) program ( x ¯ age: 73.8 years, female: 33.3%). Participants trained 3× per week, 30-60 min per session. Stepping-group differences were significant for all measures. B&S group improved in maximal step length (anterior and lateral), strength, and one functional task. Stepping group outperformed B&S group in Timed Up and Go and maximal step length posterior. B&S group outperformed stepping group in two strength measures. Exertion scores were lower for the stepping group. Overall, Divided-Attention Timed Stepping Accuracy Task training resulted in more within-group improvements and two between-group measures with less perceived effort and shorter intervention times.

Background: Persons with multiple sclerosis (MS) commonly have difficulty walking. The 6-Minute Walk Test (6MWT) assesses functional capacity but may be considered burdensome for persons with MS, especially those with higher disability levels. The 2-Minute Walk Test (2MWT) may be an alternative measure to the 6MWT. The purpose of this study was to investigate the validity of the 2MWT in persons with MS., Methods: Twenty-eight ambulatory persons with MS aged 18 to 64 years participated in this cross-sectional study. Participants completed five measures of walking performance (2MWT, 6MWT, usual and fast gait speed, and Timed Up and Go test) and two functional measures (Berg Balance Scale and five-times sit-to-stand test) during a testing session. Participants were classified into two subgroups based on Disease Steps scale classification., Results: The 2MWT was significantly correlated with the 6MWT (r = 0.947), usual gait speed (r = 0.920), fast gait speed (r = 0.942), the Timed Up and Go test (r = -0.911), and other functional measures. The 2MWT explained 89% of the variance seen during the 6MWT. The distances completed on the 2MWT and 6MWT accurately distinguished the subgroups., Conclusions: This study demonstrated good construct and discriminant validity of the 2MWT in persons with MS, providing an efficient and practical alternative to the 6MWT. Validation of the 2MWT with other functional measures further supports these findings., Competing Interests: The authors declare no conflicts of interest.

A spinal cord injury (SCI) frequently results in impaired balance, endurance, and strength with subsequent limitations in functional mobility and community participation. The purpose of this case report was to implement a training program for an individual with a chronic incomplete SCI using a novel divided-attention stepping accuracy task (DASAT) to determine if improvements could be made in impairments, activities, and participation. The client was a 51-year-old male with a motor incomplete C4 SCI sustained 4 years prior. He presented with decreased quality of life (QOL) and functional independence, and deficits in balance, endurance, and strength consistent with central cord syndrome. The client completed the DASAT intervention 3 times per week for 6 weeks. Each session incorporated 96 multi-directional steps to randomly-assigned targets in response to 3-step verbal commands. QOL, measured using the SF-36, was generally enhanced but fluctuated. Community mobility progressed from close supervision to independence. Significant improvement was achieved in all balance scores: Berg Balance Scale by 9 points [Minimal Detectable Change (MDC) = 4.9 in elderly]; Functional Reach Test by 7.62 cm (MDC = 5.16 in C5/C6 SCI); and Timed Up-and-Go by 0.53 s (MDC not established). Endurance increased on the 6-Minute Walk Test, with the client achieving an additional 47 m (MDC = 45.8 m). Lower extremity isokinetic peak torque strength measures were mostly unchanged. Six minutes of DASAT training per session provided an efficient, low-cost intervention utilizing multiple trials of variable practice, and resulted in better performance in activities, balance, and endurance in this client.

Background and Objectives: This multicentre, open-label study investigated the safety and efficacy of Gammaplex, a 5% Intravenous Immunoglobulin (IVIg), in patients with idiopathic (immune) thrombocytopenic purpura (ITP)., Materials and Methods: Patients were between the ages of 6 and 70 years; had ITP for at least six months and had a platelet count ≤ 20 × 10(9)/L. Eligible patients were dosed with 1 g/kg of Gammaplex on two consecutive days, followed by assessment of safety and efficacy on Days 3, 5, 9, 14, 21, 32 and 90. Response was defined as the increase in platelet count to a threshold of ≥ 50 × 10(9)/L on or before Day 9 after the first dose of Gammaplex., Results: All 35 patients received at least one infusion of Gammaplex. Twenty-nine (83%) patients responded to Gammaplex, similar to the historical control, with a 95% lower one-sided confidence interval of 68.9%. Median duration of response was 10.0 days, with an overall reduction in bleeding episodes. Gammaplex provided supranormal concentrations of total IgG; mean peak concentration (Cmax) of 45.3 g/L (4.53 g/dL), with a mean half-life of 28.5 days. Fifteen patients reported 63 Adverse Drug Reactions (ADRs); the most common were headache (10 patients), vomiting (6 patients) and pyrexia (5 patients). Five of these ADRs were considered serious, one patient had three concurrent Serious Adverse Events (SAEs); these were vomiting, dehydration and headache. Two other patients each had one SAE (headache). There were no unexpected Adverse Events (AEs) or thromboembolic episodes and no significant changes in vital signs, biochemical, haematological and virology results., Conclusion: Gammaplex achieved a very high concentration of serum IgG but was well-tolerated and effective in the treatment of ITP with a similar degree of efficacy to the pre-determined historical control group and the pre-set statistical criteria., Trial Registration: ClinicalTrials.gov NCT00504075 Clinical Trials Registry India 000016.

This open-label multi-centre study evaluated a new intravenous immunoglobulin, Gammaplex®, in the treatment of 50 patients with primary immunodeficiency and significant hypogammglobulinaemia. Patients treated previously with other intravenous immunoglobulins received Gammaplex® on their same infusion schedule for 1 year; 22 were on a 21-day and 28 on a 28-day regimen (300-800 mg/kg/infusion). There were no serious, acute bacterial infections, whereas six subjects (12·0%) had at least one such infection in the 6 months before enrollment. Forty subjects (80·0%) had at least one non-serious infection; the median number of infective episodes per subject per year was 3·07. Antibiotics were taken by 38 subjects therapeutically and prophylactically by 16 at some time. Fewer than half (46·0%) missed any time off work or school because of infection or other illness. Trough immunoglobulin (Ig)G levels were above 6·00 g/l in all subjects at all assessments after 15 weeks with two exceptions. Overall, 21·2% of infusions were associated with an adverse event up to 72 h after infusion. The frequency of adverse events increased with infusion rate. Headache was the most common product-related adverse event (7·5% of 703 infusions). In conclusion, Gammaplex® is effective in primary immunodeficiency and is well tolerated., (© 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.)

The amino acid sequences of human and murine haemopoietins have been analysed using algorithms predictive for secondary structure. The results for 19 of these proteins (human and murine interleukins 2, 3, 4, 5, 6, 7 and granulocyte, macrophage and granulocyte macrophage-colony stimulating factors as well as human erythropoietin) suggest that they each contain a 4-alpha-helical bundle, ca 25 A long, as a common conformational feature. The most important predictive indicator was considered to be the occurrence of quasi-repeating sequences of seven amino acids of the form (a-b-c-d-e-f-g), with apolar side chains (usually leucine) lying alternately three and four residues apart in the a and d positions. As with other proteins of known secondary structure this periodicity favours the formation of alpha-helical elements, each with an apolar external strip, which interdigitate closely with one another when tested appropriately. Molecular models based on these putative 4-alpha-helical bundles are presented--with special reference to human granulocyte macrophage-colony stimulating factor. The extent to which such models are consistent with experiments designed to delineate receptor binding sites is discussed.

Mammalian dihydroorotase (DHOase, EC 3.5.2.3) is part of a trifunctional protein, dihydroorotate synthetase which catalyzes the first three reactions of de novo pyrimidine biosynthesis. We have subcloned a portion of the cDNA from the plasmid pCAD142 and obtained a nucleotide sequence which extends 2.1 kb in the 5' direction from the sequence encoding the aspartate transcarbamoylase (ATCase) domain at the 3'-end of the cDNA. The DHOase and ATCase domains have been purified from an elastase digest of the trifunctional protein and subjected to amino acid (aa) sequencing from their N termini. The sequence of the N-terminal 24 aa of the DHOase domain has been obtained and aligned with the cDNA sequence. The C-terminal residues of the DHOase domain have been identified as Leu followed by Val which, when taken with partial sequences of the CNBr fragments of this domain, defines the coding sequence of the active, globular DHOase domain released by proteolysis. Prediction of protein secondary structure from the deduced aa sequence showed that the DHOase domain (Mr 37,751) is separated from the C-terminal ATCase domain (Mr 34,323) by a bridging sequence (Mr 12,532) consisting of multiple beta-turns.

The circular dichroism of bovine luteinizing hormone in the far ultraviolet (200-240 nm) and near ultraviolet (240-320 nm) is reported as a function of pH, reduction and denaturation. The significance of side-chain ellipticity in the native and fully randomised hormone is critically examined, using denatured and reduced ribonuclease and insulin as bases for comparison. Disulphide groups make no measurable contribution to the side-chain ellipticity. Judged by the spectra of the subunits both isolated and recombined, those treatments which promote subunit disociation without causing chain unfolding, reversibly decrease the ellipticity in the near ultra-violet with minimal effect in the far ultraviolet. Thermal perturbation difference spectroscopy of bovine luteinizing hormone and its subunits shows that, in common with the ovine and porcine hormones, there are two tyrosine residues located at the interface between the subunits and inaccessible to water. Only two or three of the five water-accessible tyrosine residues are reactive to N-acetylimidazole.

The N-acetyl(Aib)nN'-methylamides (with n = 1, 2 and 3) and the N-acetyl-(Aib)3 methyl ester have been synthesized using an oxazolone procedure. An experimental conformational analysis of this series of oligomers has been carried out in water, DMSO-d6 and CDCl3 using n.m.r. techniques, and in chloroform using i.r. spectroscopy. Deuterium exchange rates of amide protons in DMSO-d6 and the rates of these proton chemical shifts with temperature in water, DMSO-d6 and CDCl3 indicate that the oligomeric N'-methylamides adopt conformations that have no hydrogen bonds when n = 1, one hydrogen bond when n = 2, and two hydrogen bonds when n = 3, and that Ac(Aib)3OMe has a conformation with one hydrogen bond. An analysis of the N-H stretching region of the i.r. spectra of these compounds in CHCl3 also suggests the existence of these conformational states. These data imply that the peptides adopt the 3(10)-helical and not the alpha-helical conformation in solution. This conclusion supports the hypothesis that the Aib residue has asymmetric geometry at the C alpha atom in solution, similar to that reported in the literature for the crystalline state.

The circular dichroism (CD) spectra of pig relaxin and pig insulin are similar, reflecting the known structural similarities between the two hormones. However, the conformational characteristics of the separate chains of insulin and relaxin show significant differences. The S-sulfo forms of insulin A and B chains and S-sulfo relaxin A chain have CD spectra consistent with largely unordered structures whereas the S-sulfo form of relaxin B-chain has at least 90% beta--structure. This beta-structure may explain the unusual solubility and adsorptive properties of the relaxin B-chain and the poor combination yields with A-chain. The relaxin B-chain changes to a largely unordered conformation if the peptide is shortened at the carboxyl terminus by six amino acid residues. This conformational change has important implications in planning relaxin synthesis strategy. Significant interactions and conformational changes are observed between the oxidized forms of the A and B chains of both relaxin and insulin. In using CD to monitor chain recombination of native relaxin peptides it was found that the spectra obtained after depending on whether the reduced chains are separated or not separated from the reaction mixture prior to reoxidation. Although the spectra differ the biological activity was 20% in both cases. The remainder of the reoxidized but inactive material contains beta-structures which make a greater contribution to the CD spectrum when the chains have been separated and processed than when they are reoxidized in situ.

Polyacrylamide resins [Atherton et al., Bioorg. Chem. 8, 351-370 (1979)] have been found suitable for solid-phase radioimmunoassay of peptides synthesised on the same supports; they are sufficiently stable during side-chain deprotection and swell sufficiently in aq. media to admit antibody molecules to the sites of peptide attachment. A re-examination of five synthetic peptide sequences corresponding to (15-21), (56-62), (94-99), (113-119) and (145-151) of beef myoglobin analogous to those delineated by Atassi [Immunochemistry 12, 423-438 (1975)] for sperm whale myoglobin shows that they all bind anti-beef myoglobin antibodies raised in rabbits, with binding capacities in the order V = III greater than IV greater than I = II. The resin-bound peptide (72-88) binds such antibodies even more extensively, as do certain sequential variants of peptide V. Other peptides, bound to polyacrylamide or polystyrene resins but unrelated to any of the five sequences and varying in size and amino acid composition and sequence were also tested with various antisera. It was concluded that the antibody binding properties of the 30 or so small peptides (two-seven residues) are dominated by their cationic and/or hydrophobic properties. In small peptides, therefore, antibody binding can be safely interpreted only in terms of general structural properties but not in terms of biological specificity. The latter property becomes assessable only with peptides representing larger areas of antigenic protein surfaces.

The technique of thermal perturbation difference spectroscopy for examining chromophores in proteins has been set on a more acceptable theoretical and experimental foundation. (i) The origins of the thermal effect have been analysed to explain changes in spectral band width and wavelength for simple chromophores in various solvents. Comparison with theoretical curves shows that the effect of heating chromophore solutions is mainly spectral broadening coupled with an almost negligible blue shift. The apparently anomalous behavior of tryptophan and tyrosine in aqueous solvents, where the main effect is a red shift on heating, is traced to hydrogen bonding with water. A model in which tyrosine acts simultaneously as H-donor (Type I) and H-acceptor (Type II) and the later is the more temperature sensitive, is successful in explaining all available data for a variety of solute derivatives and solvents. (ii) The contribution of chromophores in the protein interior has been assessed using polyvinyl alcohol films of differing water content. There models simulate the rigidity and low thermal expansivity of the protein interior and confirm that buried chromophores contribute negligibly if at all to thermal difference spectra. (iii) Curve-fitting procedures have been used for matching protein difference spectra over a wavelength range, to those for mixtures of models, rather than relying as hitherto on data measured at extrema.

Leghaemoglobin from the subclover, Trifolium subterraneum cultivar Woogenellup, has been fractionated into at least four electrophoretically distinct components using the ion-exchange chromatographic procedure described by Appleby et al. (Appebly, C.A., Nicola, N.A., Hurrell, J.G.R. and Leach, S.J. (1975) Biochemistry 14, 4444--4450) for soybean leghaemoglobins. Unlike those of soybean, the subclover leghaemoglobins showed no evidence of autoxidation under identical isolation procedures, implying that these proteins have an unusually stable ferrous oxidation state. Circular dichroism in the far-ultraviolet (200--240 nm) indicated a high helicity (approx. 70%) as has been reported for other species of leghaemoglobins. However, circular dichroism in the near-ultraviolet region (240--300 nm) indicated that the haem-protein interactions may be considerably different in the subclover leghaemoglobins and this may explain their atypical resistance to autoxidation and the absence of nicotinate binding in these proteins.

Reciprocal hybrids were constructed between human and mouse interferons (IFNs), and their antiviral activity was examined on different target cells and compared to the activity of the parental molecules. In addition, we used a number of predictive algorithms on a data base of the available alpha-interferon sequences to propose a working model for the overall conformation of the alpha-interferon molecule that is consistent with the structural predictions. Remarkable conservation within the predicted alpha-helical segments of the interferon molecule was observed. We propose that the observed changes in the activity and specificity of the hybrids obtained are largely due to the sequences present in the loops at the ends of the major helical structures; these are less conserved, contain beta-bends, and are generally hydrophilic and flexible. The data on the constructed mouse-human hybrids have shown that the activity on human cells is contributed by determinants present in the N-terminal 122 amino acids of human IFN, thus implicating one or more loops within this region (e.g. loops 1-12, 25-38, 70-74, and 103-113). The activity on bovine cells appears to be localized mainly in sequence 60-121, implicating the role of loops 70-74 and/or 103-113 of the human IFN molecule. The specificity of mouse IFN for mouse cells is in some or all of the loops (70-74, 103-113, 134-139, and 163-166) in the C-terminal sequence. The proposed working model should provide guidelines for the study of the specificity of action in molecular terms.

Structural rearrangements in sperm whale myoglobin and leghaemoglobins caused by changes in the spin or oxidation state of the iron as a consequence of ligand binding have been measured by difference spectroscopy in the ultraviolet. When compared with the high-spin acetate complex, ligands which cause a transition to the low-spin state also cause large perturbations of tyrosine(s) remote from the haem pocket in myoglobin but only minor perturbations of tryptophan (s) in leghaem calobin. This may indicate a weaker coupling between events at the haem site and conformational changes in the protein in leghaemoglobins. The absorption spectra of various haem-liganded forms of the two proteins as well as the binding of the dye rose Bengal to the two apoproteins are consistent with weaker interactions between the haem ano apoprotein and a more solvent-exposed haem pocket in leghaemoglobin compared with myoglobin.

The circular dichroism spectra of leghemoglobin a from the root nodules of soybean have been compared with those for sperm whale myoglobin in the fat- and near-ultraviolet and the Soret and visible regions of the spectrum. Circular dichroism spectra in the far-ultraviolet show that the leghemoglobins all have a high alpha-helix content (soybean leghemoglobin a, 55%) regardless of the nature of bound ligands and oxidation or spin state of the heme iron. The known sequence homologies with mammalian hemoglobins may therefore be reflected in conformational homologies as suggested by the x-ray studies of Vainshtein et al. ((1975) Nature (London) 254, 163-164) on lupin leghemoglobin. Removal of the heme moiety decreases helicity by only 9% for leghemoglobins, compared with 23% for myoglobin. This, the much smaller heme contribution to the near-ultraviolet circular dichroism than in myoglobin, and the greater accessibility of the heme moiety to aqueous solvent (Nicola et al. (1974), Proc. Aust. Biochem. Soc. 7, 21) suggest that the association between heme and protein is much weaker in leghemoglobins than in myoglobin. The aromatic Soret and visible circular dichroism spectra for all derivatives of leghemoglobin are opposite in sense to those for myoglobin, showing that the patterns of protein side chain contacts with the heme are different in the two classes of heme proteins. There is strong evidence that one of the two tryptophans whose identity and structural role in myoglobin is known, is present also in plant leghemoglobins, hydrogen-bonded and in a similar nonpolar environment whether heme is present or not. The above findings help to explain the remarkably high oxygen affinity and some other ligand-binding properties of leghemoglobins which differ from those of myoglobin.

Peptides corresponding to sequences (72-88) and (26-54) of beef myoglobin have been synthesised in their open-chain and cyclised forms (using a disulphide bridge) and tested for their antigenicity and immunogenicity. Antibodies raised to beef myoglobin bound to both peptides but more strongly to the 29-residue than to the 17-residue peptide. Cyclisation increased the antigenicity of the larger peptide. In this form the peptide competed much more strongly than in the uncyclised form for specific antibodies to beef myoglobin. The peptides are immunogenic in mice without being coupled to a protein carrier and produce antibodies which bind to beef myoglobin. Peptide (26-54) is the more immunogenic in producing a larger antibody titre to the parent myoglobin and cyclisation again enhances this property. The findings lend weight to the view that longer peptide sequences might be expected to favour the folded state, therefore binding more strongly to antibodies raised to the native protein and eliciting a population of antibodies which contain a larger proportion specific for that conformation. Cyclisation enhances antigenicity and immunogenicity presumably by decreasing the number of degrees of conformational freedom of a peptide without excluding native-like conformations.

Circular dichroism studies on leghaemoglobins from snake bean, lupin, serradella and other plants show that, in common with soybean (reported earlier) they have a similar overall polypeptide chain conformation and haem environment and orientation. Immunochemical studies, on the other hand, suggest that the antigenic determinants on the surface of the leghaemoglobins vary considerably. Thus, firstly the alpha-helix content of the leghaemoglobins as a class is very similar (60-65%) and approaches that of the myoglobins, secondly, the sign, magnitude and shape of their circular dichroism spectra in the near ultraviolet, Soret and visible regions suggest close similarities in the environment and orientation of a structurally important tryptophan residue and of the haem moiety, and thirdly, there is comparatively weak haem-protein interaction. The extent of immuno cross-reactivity was found to be best deomonstrated using the Farr radioimmunoassay procedure. The results were (a) 5 leghaemoglobins from one plant (soybean) crossreacted completely but with varying affinities. (b) The extent of cross reactivity between leghaemoglobins from different plants was compared to that within a single plant; the reaction of antiserum to a soybean leghaemoglobin with a serradella leghaemoglobin was weak, with a snake bean leghaemoglobin still weaker (and incomplete) while lupin leghaemoglobins showed no cross reactivity at all. (c) The "rapid" attenuation of cross reactivity among different plant leghaemoglobins is explicable in terms of the extensive amino acid substitutions which have been demonstrated in the literature and in the present studies. (d) In view of this rapid divergence it is not surprising that sperm whale and horse heart myoglobins showed no cross reactivity with soybean leghaemoglobins. In summary, amino acid substitutions in the leghaemoglobin family are conformationally but not immunochemically conservative.

The conformational motilities of three regions of the sperm whale myoglobin molecule and of an isolated peptide of myoglobin have been examined by measuring the equilibrium constant for the native equilibrium nonnative transition. The immunological approach of Furie et al. (Furie, B., Schechter, A.N., Sachs D., and Anfinsen, C.B. (1975), J. Mol. Biol.92, 497-506) was used with convenient modifications. Antibodies specific to the nonnative conformations were used in assaying for competition between the radioactively labeled peptide and native myoglobin. Labeling was by 125I iodination of the peptide or its 3-(4-hydroxyphenyl)propionyl derivative, and separation of the immune complex from the free peptide was either by ammonium sulfate precipitation or by centrifugation of the antibodies immobilized on Agarose beads. For the antigenic regions of the sequence (1-55), the measured conformational equilibrium constant was 840 +/- 200 at 22 degrees C; the value for the C-terminal region (132-153) was 280 +/- 120 at 25 degrees C, while that for the region (66-76) adjacent to the heme group was greater than 2.5 x 10(6). Measurements on the isolated peptide (132-153) indicated that 1% of the molecules adopt native-type folding in aqueous solution at 36 degrees C.

Some 30 cytokine amino acid sequences (mainly interleukins, colony stimulating factors and tumor necrosis factors) have been examined for evidence of secondary structure as well as longer-range interactions of a type likely to lead to stable alpha-helical bundles. Most, though not all, of the cytokines examined have a high predicted alpha-helical content (40-60%) and quasi-repeating heptads containing i/i + 3 apolar periodicities. This major subset of the cytokines is predicted to be characterized by molecules in which 4-alpha-helical bundles with an average length of 25A are the most marked conformational features. Based on these conclusions, we suggest structures for huG-CSF, huGM-CSF and muIL-5 in which defined loop segments at the ends of helical bundles are the most likely sites for binding and recognition by specific cell receptors. As such, they provide a means for testing or refining the three working models we have defined, using currently available methods of site-directed substitution and deletion mutagenesis, as well as synthetic peptides corresponding to the proposed loop sequences and the use of monoclonal antibodies of defined epitopic specificity. The structure arrived at for huGM-CSF is consistent with the limited data currently available concerning the residues which are important for binding and activity.

The conformational properties of the N-acetyl-N'-methylamides of the dipeptides lysyl-lysine, lysyl-tyrosine, tyrosyl-lysine, and tyrosyl-tyrosine were studied by means of conformational energy calculations, by n.m.r. measurements in deuterated dimethylsulfoxide, and by circular dichroism in water, methanol, dioxane-water, and trifluoroethanol. Since these four dipeptides occur occasionally as bends in proteins, it was of interest to see whether short-range interactions, acting within the terminally blocked dipeptides, are sufficient to stabilize bend conformations significantly over other conformations. It was found that the four dipeptides exist as ensembles of conformations in solution. Therefore, it appears that longer-range interactions, such as those present in proteins, are required if bend conformations of these dipeptide sequences are to exist as stable conformations. Three of the dipeptides behave rather similarly. Both the CD and the n.m.r. experiments and computations indicate that the fourth (Lys-Tyr) differs from the others. It has a preference for compact conformations that appear to be stabilized by strong favorable interactions, primarily hydrogen bonds, between the tyrosyl and the lysyl side chains. The computations suggest that the presence of these interactions, and hence the existence of preferred conformations, is strongly solvent-dependent, and that these interactions are weakened in aqueous solution.