Conformational studies of 3,4-dideoxy furanoid sugar amino acid containing analogs of the receptor binding inhibitor of vasoactive intestinal peptide

被引：19

作者：

Chakraborty, TK

Reddy, VR

Sudhakar, G

Kumar, SU

Reddy, TJ

Kumar, SK

Kunwar, AC

Mathur, A

Sharma, R

Gupta, N

Prasad, S

机构：

[1] Indian Inst Chem Technol, Bioorgan Lab, Organ Div 3, Hyderabad 500007, Andhra Pradesh, India

[2] Dabur Res Fdn, Sahibabad 201010, Ghaziabad, India

来源：

TETRAHEDRON | 2004年 / 60卷 / 38期

关键词：

3,4-dideoxy furanoid sugar amino acids; VIP receptor; conformation; NMR;

D O I：

10.1016/j.tet.2004.07.032

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Conformational analysis of vasoactive intestinal peptide (VIP) receptor binding inhibitor Leu(1)-Met(2)-Tyr(3) -Pro(4)-Thr(5)-Tyr(6)-Leu(7)-Lys(8) 1 by various NMR techniques and constrained molecular dynamics (MD) simulation studies revealed that the molecule had a turn structure involving its Tyr(3)-Pro(4)-Thr(5)-Tyr(6) moiety with intramolecular hydrogen bond between Tyr(6)NH-->Tyr(3)CO. In order to mimic the structure of 1, peptidomimetic analogs 2-4 were synthesized using conformationally constrained scaffolds of 3,4-dideoxy furanoid sugar amino acids (2S,5R)-ddSaa1 5 and its enantiomer (2R,5S)-ddSaa2 6. All these analogs displayed well defined three-dimensional structures akin to that found in 1. Peptides 2 and 3, which differed only in the sugar amino acid stereochemistry, show propensity of structures with identical intramolecular hydrogen bonds between ThrNH --> MetCO. A similar structure with a hydrogen bond between TyrNH --> MetCO was observed in 4. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：8329 / 8339

页数：11

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