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Absolute configuration for peptidomimetic residues in bioactive peptides
Author(s) -
Yamazaki Toshimasa,
Goodman Murray
Publication year - 1991
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530030410
Subject(s) - chemistry , peptidomimetic , absolute configuration , stereochemistry , combinatorial chemistry , peptide , biochemistry
A modern method is reported for the assignment of absolute configuration for peptidomimetics in bioactive peptides by use of 1 H‐NMR parameters in solution. Four peptide systems incorporating either retro‐inverso modifications or 2‐aminocyclopentanecarboxylic acid (2‐Ac 5 c) as a peptidomimetic for proline are discussed. (1) Two 14‐membered cyclic dermorphin analogs Tyr‐c[ D ‐A 2 bu‐Phe‐gPhe‐(S and R)‐mLeu] with a reverse amide bond between gPhe and mLeu residues where gPhe denotes a gem ‐diamino analog of Phe and mLeu refers to a malonyl analog of Leu. (2) Two cyclic hexapeptides related to somatostatin, c[gSar 6 ‐(S and R)‐mPhe 7 ‐ D ‐Trp 8 ‐Lys 9 ‐Thr 10 ‐Phe 11 ], with a reverse amide bond between the gSar and mPhe residues where the gSar and mPhe denote the gem ‐diamino and malonyl analogs of the Sar and Phe residues, respectively. The superscript numbers refer to positions in native somatostatin. (3) Cyclic hexapeptide somatostatin analogs containing 2‐Ac 5 c [ trans ‐(1S,2S)‐2‐Ac 5 c, trans ‐(1R,2R)‐2‐Ac 5 c, cis ‐(1R,2S)‐2‐Ac 5 c, and cis ‐(1S,2R)‐2‐Ac 5 c] in place of proline c[(2‐Ac 5 c) 6 ‐Phe 7 ‐ D ‐Trp 8 ‐Lys 9 ‐Thr 10 ‐Phe 11 ]. (4) Morphiceptin related analogs incorporating a cis ‐2‐Ac 5 c residue as shown in Tyr‐ cis ‐2‐Ac 5 c‐Phe‐Val‐NH 2 . The methodology described in this investigation could be applied to a wide variety of peptide systems.