Exploring the interest of 1,2-dithiolane ring system in peptide chemistry. Synthesis of a chemotactic tripeptide and x-ray crystal structure of a 4-amino-1,2-dithiolane-4-carboxylic acid derivative.
Due to their relevant biological functions and specific chemical reactivity 1,2-dithiolanes (five-membered cyclic disulfides) represent an emerging class of heterocyclic compounds. However, despite the extensive research centered on lipoic acid and its analogues, only very few data are at the present available on peptides containing this ring system. We report here synthesis, conformation and bioactivity of a fMLF-OMe analogue, namely For-Met-Adt-Phe-OMe (7), in which the residue of the 4-amino-1,2-dithiolane-4-carboxylic acid (Adt) (4) replaces the central L-leucine. The crystal conformation of the synthetic intermediate Boc-Adt-OMe (5) is also described and compared to that of lipoic acid (R-1,2-dithiolane-3-pentanoic acid) (3) and asparagusic acid (1,2-dithiolane-4-carboxylic acid) (2).
Morera
Enrico
E
Dipartimento di Studi Farmaceutici and Centro di Studio per la Chimica del Farmaco del CNR, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185, Rome, Italy.
Lucente
Gino
G
Ortar
Giorgio
G
Nalli
Marianna
M
Mazza
Fernando
F
Gavuzzo
Enrico
E
Spisani
Susanna
S
D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000737:chemistry*
C448825:1,2-dithiolane; D002630:Chemotactic Factors; D009842:Oligopeptides; D008063:Thioctic Acid