A. D'Ursi et al., Solution conformation of a potent cyclic analogue of tuftsin: Low-temperature nuclear magnetic resonance study in a cryoprotective mixture, J MED CHEM, 42(10), 1999, pp. 1705-1713
Tuftsin, a linear tetrapeptide (Thr-Lys-Pro-Asg), corresponding to the sequ
ence 289-292 of the heavy chain of leukokinin, has been the object of inten
sive SAR studies during the past 30 years, owing to its numerous biological
activities and to the possibility of generating a novel anticancer drug. A
cyclic tuftsin analogue, c-[T-K-P-R-G], has biological activity 50 times h
igher than that of the parent linear peptide. Here we present a conformatio
nal study of c-[T-K-PR-G] based on NMR data in a cryoprotective DMSO/water
mixture. The preferred conformation is a type Via turn centered on the K-P
residues. The orientation of the side chains of the two basic residues (K a
nd R) may represent the essential feature of the bioactive conformation of
tuftsin. A possible role of tuftsin as a DNA binding motif is suggested by
the similarity of the bioactive conformation of c-[T-K-P-R-G] and of the be
ta-turn conformation proposed by Suzuki for the [T, S]-P-K-R motif.