Chemical synthesis of Maxadilan, a non-mammalian potent vasodilatory peptide consisting of 61 amino acids with two disulfide bridges, and its related peptides

Nokihara Kiyoshi

Yasuhara Tadashi

Nakata Yoshihiro

Lerner Ethan A.

Wray Victor

International Journal of Peptide Research and Therapeutics

A potent and persistent non-mammalian derived vasodilator, maxadilan (Maxa) consists of 61 amino acids with two disulfide linkages and acts as an agonist of the type I receptor of pituitary adenylate cyclase activating polypeptide (PACAP), although there is very little sequence similarity. The total chemical syntheses of Maxa, its disulfide isomers and various fragments have been performed successfully by highly efficient solid-phase peptide synthesis (SPPS). A "difficult sequence", envisaged in the middle region of Maxa, could be overcome by improved synthesis protocols. After assembly peptides were liberated from the resin by cleavage. Peptides having disulfide(s) were purified by two steps of preparative HPLC using cation exchange followed by reverse phase columns. Purified peptides were characterized by HPLC, Edman-sequencing, amino acid analysis and mass spectrometry in addition to disulfide form determination. The peptides obtained were used for recognition studies by the melanophore assay to confirm the native disulfide form. Peptide libraries related to Maxa, produced in the present study, will be useful for the elucidation of the structural requirements of Maxa for interaction with the PACAP type 1 receptor (PAC1).

vasodilator

maxadilan

PAC1 receptor

disulfide isomer

highly efficient solid-phase synthesis

difficult sequence

melanophore assay

Medical sciences [ 490 ]

eng

Springer

Copyright (c) 2007 Springer "The original publication is available at www.springerlin.com"

[ISSN] 1573-3149

[DOI] 10.1007/s10989-007-9097-9

[NCID] AA12077391

[DOI] http://dx.doi.org/10.1007/s10989-007-9097-9