Conformational modifications of cyclic hexapeptide somatostatin analogs

Wiley - Tập 23 Số 2 - Trang 142-150 - 1984
Roger Freidinger1, Debra S. Perlow1, William C. Randall1, Richard Saperstein2, Byron H. Arison2, Daniel F. Veber1
1Merck Sharp&Dohme Research Laboratories, West Point, PA
2Merck Sharp&Dohme Res. Lab., Rahway, NJ, USA

Tóm tắt

A model for the bioactive conformation of the highly active cyclic hexapeptide somatostatin analog cyclo‐(Pro‐Phe‐d‐Trp‐Lys‐Thr‐Phe) has been proposed. As a test of this model, several compounds containing lactam and N‐Me amino acid conformational modifications in the Thr‐Phe‐Pro‐Phe beta turn were synthesized. The N‐Me alanine and sarcosine substitutions for proline gave highly active analogs, while lactam dipeptides in place of Phe‐Pro decreased potency. 1H n.m.r. and CD spectra of these analogs illustrate the conformational effects in solution of these modifications. The results provide additional support for the proposed conformational model.

Từ khóa


Tài liệu tham khảo

10.1038/292055a0

Veber D.F., 1981, Proceedings of the Seventh American Peptide Symposium, 685

Freidinger R.M., 1981, Proceedings of the Seventh American Peptide Symposium, 673

10.1021/jo00340a023

10.1021/jm00191a026

10.1073/pnas.75.6.2636

10.1016/0045-2068(78)90035-4

10.1002/bip.360101108

Veber D.F., 1983, Proceedings of the Seventeenth European Peptide Symposium, 789

10.1021/jo00953a021

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Wiley

Tập 23 Số 2

142-150

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