Conformational comparisons of a series of tachykinin peptide analogs

Title

Conformational comparisons of a series of tachykinin peptide analogs

Creator

Beard D J; Perrine S A; Phillips E; Hoque S; Conerly S; Tichenor C; Simmons M A; Young J K

Publisher

Journal of Medicinal Chemistry

Date

2007
2007-12

Description

Previous studies have shown differences in the biological activity and the structure of two naturally occurring tachykinin peptides, substance P (SP, RPKPQQFFGLM-NH2),and ranatachykinin C (RTKC, HNPASFIGLM-NH2). To further understand the basis for these differences, four analogs that selectively incorporate the amino acid differences between SP and RTKC have been synthesized for study. The four peptide analogs studied have the following amino acid sequences: SP2-11, also known as des-Arg SP (PKPQQFFGLM-NH2); Q5A-SP (RPKPAQFFGLM-NH2); Q6S-SP (RPKPQSFFGLM-NH2); and Q5AQ6S-SP (RPKPASFFGLM-NH2). Nuclear magnetic resonance spectroscopy and molecular modeling calculations were performed on SP, RTKC, SP2-11, Q5A-SP, Q6S-SP, and Q5AQ6S-SP to compare their conformational differences and similarities in the presence of the membrane mimetic system sodium dodecyl sulfate. The molecular modeling data of the analogs Q5A-SP and Q6S-SP show residues 1-3 have a random conformation and residues 4-8 have a helical structure, while the C-terminus contains a poly C-7 conformation that is similar to SP but different from RTKC., The molecular modeling data of the analogs SP2-11 and Q5AQ6S-SP show a continuous helix conformation for residues 4-11 at the C-terminus, which is different from SP but similar to RTKC. These structural differences are related to the functional differences of binding of the peptides at the SP receptor (NK1).

Subject

Pharmacology & Pharmacy; escherichia-coli; nmr; dynamics; nuclear-magnetic-resonance; substance-p receptor; agonists; neuropeptides; bradykinin; molecular modeling investigations; sds micelles

Identifier

Format

Journal Article or Conference Abstract Publication

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

6501-6506

Issue

26

Volume

50

Citation

Beard D J; Perrine S A; Phillips E; Hoque S; Conerly S; Tichenor C; Simmons M A; Young J K, “Conformational comparisons of a series of tachykinin peptide analogs,” NEOMED Bibliography Database, accessed September 28, 2021, https://neomed.omeka.net/items/show/8596.

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