In:
International Journal of Peptide and Protein Research, Wiley, Vol. 46, No. 3-4 ( 1995-09), p. 221-227
Abstract:
In order to study the role of the amino acid in position B25 and its environment in shortened insulins, a series of analogues was prepared with the following modifications; 1, Stepwise shortening of the B‐chain including replacements of Tyr B26 and Thr B27 by glycine; 2, substitutions at the carboxamide nitrogen of des‐(B26‐B30)‐insulin‐B25‐amide by apolar, polar or charged residues of various chain lengths; 3, replacement of Phe B25 by asparagine‐amide, phenylalaninol or a series of alkyl and aralkyl residues. Trypsin‐catalyzed semisyntheses were performed with Boc‐protected or unprotected des‐octapeptide‐(B23‐B30)‐insulin and synthetic peptides. Relative receptor binding and in vitro bioactivity of [Asn B25 ]‐des‐(B26‐B30)‐insuIin‐B25‐amide was 227 and 292% (on insulin), other activities ranged between 1 and ca. 200%. We make the following conclusions. An l ‐amino acid is essential in position B25. The B25‐carbonyl and NH groups favour high binding and “superpotency”, but are not indispensible for receptor contacts. For high affinity receptor interaction, the planarity at the C 2 ‐atom and the distance of B25‐side‐chain branching in position B25 are important, but an aromatic ring is not necessary.
Type of Medium:
Online Resource
ISSN:
0367-8377
DOI:
10.1111/jpp.1995.46.issue-3-4
DOI:
10.1111/j.1399-3011.1995.tb00593.x
Language:
English
Publisher:
Wiley
Publication Date:
1995
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