Combined solid-phase/solution synthesis of a 31-residue vasoactive intestinal peptide analog: general method for repetitive coupling of fragments without isolation and purification of intermediates
| Autor: | J. Michalewsky, Z. Zhao, Edgar P. Heimer, Mushtaq Ahmad, Wen Liu, Arthur Felix, A. Daniewski, Theodore Lambros |
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| Rok vydání: | 1998 |
| Předmět: |
Chemistry
Vasoactive intestinal peptide Molecular Sequence Data Diastereomer Convergent synthesis Combinatorial chemistry Biochemistry Coupling reaction Peptide Fragments chemistry.chemical_compound Endocrinology Yield (chemistry) Hexafluorophosphate Lactam Trifluoroacetic acid Organic chemistry Amino Acid Sequence Vasoactive Intestinal Peptide |
| Zdroj: | The journal of peptide research : official journal of the American Peptide Society. 52(2) |
| ISSN: | 1397-002X |
| Popis: | A novel analog of vasoactive intestinal peptide (VIP) has been reported which exhibits high potency and enhanced duration of in vivo biological activity. This VIP analog, cyclo-(Lys21-Asp25)Ac[Glu8 Lys12 Nle17 Ala19, Asp25 Leu26,Lys27,28,Gly29,30,Thr31]-VIP, which also has a lactam bridge, has been reported to have relaxant effects that are significantly more potent than other beta-agonists such as salbutamol and salmeterol. Because it has potential use for the treatment of bronchial asthma in humans, various convergent syntheses were evaluated to enable the economic preparation of large quantities of this medium-sized hentriacontapeptide. From these studies we developed a combined solid-phase/solution synthesis which uses four protected fragments (each prepared by solid-phase synthesis with highly acid-labile resins) possessing Nalpha-9-fluorenylmethyloxycarbonyl and side-chain tert-butyl protection. Only equivalent amounts of each fragment were required to achieve near-quantitative coupling reactions using N-[(1H-benzotriazol-1-yl)(dimethylamino)methylene]-N-methylmeth anaminium hexafluorophosphate N-oxide/N-hydroxybenzotriazole. All reagents and side products were removed at each stage by simple extraction procedures. Final deprotection was carried out with 90% trifluoroacetic acid. Under these conditions only low levels of epimerization were observed ( |
| Databáze: | OpenAIRE |
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