4 results on '"Shirangi, Mehrnoosh"'
Search Results
2. Acylation of arginine in goserelin-loaded PLGA microspheres
- Author
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Shirangi, Mehrnoosh, Hennink, Wim E., Somsen, Govert W., Van Nostrum, Cornelus F., Pharmaceutics, Sub General Pharmaceutics, Sub Drug delivery, Dep Farmaceutische wetenschappen, Pharmaceutics, Sub General Pharmaceutics, Sub Drug delivery, Dep Farmaceutische wetenschappen, AIMMS, and BioAnalytical Chemistry
- Subjects
Arginine ,Acylation ,Lysine ,Pharmaceutical Science ,Peptide ,02 engineering and technology ,030226 pharmacology & pharmacy ,Mass Spectrometry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Polylactic Acid-Polyglycolic Acid Copolymer ,Taverne ,Controlled release ,Lactic Acid ,Guanidine ,Glycolic acid ,chemistry.chemical_classification ,Chromatography ,PLGA ,General Medicine ,021001 nanoscience & nanotechnology ,Microspheres ,LC-MS ,chemistry ,Goserelin ,0210 nano-technology ,Peptides ,SDG 6 - Clean Water and Sanitation ,Polyglycolic Acid ,Chromatography, Liquid ,Biotechnology - Abstract
Acylation of peptides is a well-known but unwanted phenomenon in polyester matrices such as poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres used as controlled release formulations. Acylation normally occurs on lysine residues and the N-terminus of the peptide. The purpose of the present work was to assess other possible acylation sites on peptides. Goserelin was used as a model peptide that lacks lysine and a free N-terminus, but contains other nucleophilic residues, i.e. serine, tyrosine and arginine, which potentially can be acylated. Goserelin loaded PLGA microspheres were prepared by a double emulsion solvent evaporation technique. Liquid chromatography ion-trap mass spectrometry (LC-ITMS) was used for determining and monitoring acylation of released goserelin. It is demonstrated that arginine is subjected to acylation with glycolic acid and lactic acid units of PLGA, which was followed by loss of NH3 from the guanidine group to obtain 2-oxazolin-4-one and 5-methyl-2-oxazolin-4-one residues with masses that are 41 and 55 Da higher, respectively, than the native goserelin. There was no evidence for acylation of serine and tyrosine in goserelin. Our results demonstrate that beside lysine also acylation of arginine can occur in peptides and proteins that are loaded and released from PLGA matrixes.
- Published
- 2016
3. Methyleneation of peptides by N, N, N, N -tetramethylethylenediamine (TEMED) under conditions used for free radical polymerization: A mechanistic study
- Author
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Shirangi, Mehrnoosh, Sastre Toraño, Javier, Sellergren, Börje, Hennink, Wim E., Somsen, Govert W., Van Nostrum, Cornelus F., Biomolecular Analysis, Pharmaceutics, Sub General Pharmaceutics, Sub Biomolecular analysis, Sub Drug delivery, Biomolecular Analysis, Pharmaceutics, Sub General Pharmaceutics, Sub Biomolecular analysis, Sub Drug delivery, BioAnalytical Chemistry, and AIMMS
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Free Radicals ,Radical polymerization ,Lysine ,Biomedical Engineering ,Pharmaceutical Science ,Peptide ,Bioengineering ,Polymerization ,chemistry.chemical_compound ,Residue (chemistry) ,Peptide Library ,Taverne ,Organic chemistry ,Amino Acid Sequence ,In situ polymerization ,chemistry.chemical_classification ,Pharmacology ,Protein Stability ,Chemistry ,Organic Chemistry ,Tetramethylethylenediamine ,Ethylenediamines ,Combinatorial chemistry ,Molecular Weight ,Ammonium Sulfate ,Sodium bisulfite ,Peptides ,SDG 6 - Clean Water and Sanitation ,Biotechnology - Abstract
Free radical polymerization is often used to prepare protein and peptide-loaded hydrogels for the design of controlled release systems and molecular imprinting materials. Peroxodisulfates (ammonium peroxodisulfates (APS) or potassium peroxodisulfates (KPS)) with N,N,N,N-tetramethylethylenediamine (TEMED) are frequently used as initiator and catalyst. However, exposure to these free radical polymerization reagents may lead to modification of the protein and peptide. In this work, we show the modification of lysine residues by ammonium peroxodisulfate (APS)/TEMED of the immunostimulant thymopentin (TP5). Parallel studies on a decapeptide and a library of 15 dipeptides were performed to reveal the mechanism of modification. LC-MS of APS/TEMED-exposed TP5 revealed a major reaction product with an increased mass (+12 Da) with respect to TP5. LC-MS2 and LC-MS3 were performed to obtain structural information on the modified peptide and localize the actual modification site. Interpretation of the obtained data demonstrates the formation of a methylene bridge between the lysine and arginine residue in the presence of TEMED, while replacing TEMED with a sodium bisulfite catalyst did not show this modification. Studies with the other peptides showed that the TEMED radical can induce methyleneation on peptides when lysine is next to arginine, proline, cysteine, aspargine, glutamine, histidine, tyrosine, tryptophan, and aspartic acid residues. Stability of peptides and protein needs to be considered when using APS/TEMED in in situ polymerization systems. The use of an alternative catalyst such as sodium bisulfite may preserve the chemical integrity of peptides during in situ polymerization.
- Published
- 2015
4. Identification and Assessment of Octreotide Acylation in Polyester Microspheres by LC–MS/MS
- Author
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Shirangi, Mehrnoosh, Hennink, Wim E., Somsen, Govert W., Van Nostrum, Cornelus F., Sub Drug delivery, Dep Farmaceutische wetenschappen, UIPS - Utrecht Institute for Pharmaceutical Sciences, Pharmaceutics, BioAnalytical Chemistry, AIMMS, Sub Drug delivery, Dep Farmaceutische wetenschappen, UIPS - Utrecht Institute for Pharmaceutical Sciences, and Pharmaceutics
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Polyesters ,Octreotide ,Pharmaceutical Science ,Tandem mass spectrometry ,Microsphere ,Acylation ,chemistry.chemical_compound ,Polylactic Acid-Polyglycolic Acid Copolymer ,LC–MS/MS ,Tandem Mass Spectrometry ,Lc ms ms ,medicine ,acylation ,Pharmacology (medical) ,Lactic Acid ,LC-MS/MS ,Glycolic acid ,Pharmacology ,Chromatography ,Organic Chemistry ,technology, industry, and agriculture ,Microspheres ,Lactic acid ,Polyester ,chemistry ,aliphatic polyester ,Molecular Medicine ,SDG 6 - Clean Water and Sanitation ,Polyglycolic Acid ,octreotide ,Chromatography, Liquid ,Research Paper ,medicine.drug ,Biotechnology - Abstract
Purpose Polyesters with hydrophilic domains, i.e., poly(d,l-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and a multiblock copolymer of poly(ε-caprolactone)-PEG-poly(ε-caprolactone) and poly(l-lactide) ((PC-PEG-PC)-(PL)) are expected to cause less acylation of encapsulated peptides than fully hydrophobic matrices. Our purpose is to assess the extent and sites of acylation of octreotide loaded in microspheres using tandem mass spectrometry analysis. Methods Octreotide loaded microspheres were prepared by a double emulsion solvent evaporation technique. Release profiles of octreotide from hydrophilic microspheres were compared with that of PLGA microspheres. To scrutinize the structural information and localize the actual modification site(s) of octreotide, liquid chromatography ion-trap mass spectrometry (LC-ITMS) was performed on the acylated adducts. Results Hydrophilic microspheres showed less acylated adducts in comparison with PLGA microspheres. LC-MS/MS showed that besides the N-terminus and primary amine of lysine, the primary hydroxyl of the end group of octreotide was also subjected to acylation. Nucleophilic attack of the peptide can also occur to the carbamate bond presented in (PC-PEG-PC)-(PL) since 1,4-butanediisocyanate was used as the chain extender. Conclusions Hydrophilic polyesters are promising systems for controlled release of peptide because substantially less acylation occurs in microspheres based on these polymers. LC-ITMS provided detailed structural information of octreotide modifications via mass analysis of ion fragments. Electronic supplementary material The online version of this article (doi:10.1007/s11095-015-1685-3) contains supplementary material, which is available to authorized users.
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