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The success of antibody therapeutics is strongly influenced by their multifunctional nature that couples antigen recognition mediated by their variable regions with effector functions and half-life extension mediated by a subset of their constant regions. Nevertheless, the monospecific IgG format is not optimal for many therapeutic applications, and this has led to the design of a vast number of unique multispecific antibody formats that enable targeting of multiple antigens or multiple epitopes on the same antigen. Despite the diversity of these formats, a common challenge in generating multispecific antibodies is that they display suboptimal physical and chemical properties relative to conventional IgGs and are more difficult to develop into therapeutics. Here we review advances in the design and engineering of multispecific antibodies with drug-like properties, including favorable stability, solubility, viscosity, specificity and pharmacokinetic properties. We also highlight emerging experimental and computational methods for improving the next generation of multispecific antibodies, as well as their constituent antibody fragments, with natural IgG-like properties. Finally, we identify several outstanding challenges that need to be addressed to increase the success of multispecific antibodies in the clinic.

Competition horses are susceptible to high stress levels. Lavender aromatherapy (LA) is legal, has the potential to reduce stress, and is a relatively unexplored area of equine physiology. We hypothesis that LA has positive effects on helping horses cope with stress. We predict that these effects can be measured in lowered cortisol, norepinephrine, and heart rate levels in horses that have been subjected to lavender aromatherapy during a stressor. Eight horses were used in a crossover study and were transported for 15 minutes in a horse trailer. During the trailer ride (stressor), the horses received water aromatherapy as the control, and LA as the treatment. Three measurements of heart rates and blood draws were taken on each horse: (1) baseline—before loading into the trailer, (2) stressed—immediately after the trailer ride, and (3) recovery—50 minutes after the trailer ride. The blood samples were used to quantify serum cortisol levels. In both the control and treatment horses, the average difference between the baseline and stressed measurements of heart rate (HR) and cortisol increased when the horses were transported (control HR = 10.6 b/m ± 2.6 standard error [SE]; treatment HR = 9.3 b/m ± 2.6 SE; control cortisol = 3,747.2 pg/uL ± 864.2 SE; treatment cortisol = 2,511.8 pg/uL ± 1009.9 SE). In the control and treatment horses, there was no difference in the HRs of the control and treatment horses (P-value = .37); there was a difference in cortisol levels (P = .038), which provides evidence to conclude that cortisol levels were lower in horses that were subjected to LA during a stressor.

Integrative, research-based experiences have shown tremendous potential as effective pedagogical approaches. Pharmaceutical development is an exciting field that draws heavily on organic chemistry and biochemistry techniques. A capstone drug synthesis/analysis laboratory is described where biochemistry students synthesize azo-stilbenoid compounds and test the biological activity of those compounds as well as a known inhibitor on mushroom tyrosinase using UV/vis-based kinetic assays. In this paper, three such successful azo-stilbenoid inhibitors of tyrosinase, representative student generated data, technical aspects of the experiments, and an interpretation of student feedback on the project as a whole are presented.

Colchicine analogues in which an azo group is incorporated into a molecule containing the key pharmacophore of colchicine, have found particular utility as switchable tubulin binding chemotherapeutics. Combretastatin is a related compound containing a stilbene fragment that shows different bioactivity for the cis and trans isomers. We have performed cell assays on 17 new compounds structurally related to a previously reported azo-analogue of combretastatin. One of these compounds showed enhanced potency against HeLa (IC50 = 0.11 μM) and H157 cells (IC50 = 0.20 μM) for cell studies under 400 nm irradiation and the highest photoactivity (IC50 with irradiation/IC50 in dark = 550). We have performed docking and physicochemical studies of this new compound (7). Kinetic studies in water reveal a longer half-life for the cis isomer of 7 which may be one factor responsible for the better IC50 values in cell assays and the improved photoresponsive behavior.