A proposed bioactive conformation of Peptide T

The conformational profiles of Peptide T, (5–8)Peptide T, [Abu5](4–8)Peptide T and (4–8)Peptide T were computed independently to assess the geometrical characteristics of the bioactive conformation of Peptide T. The conformational profiles of the peptides were computed within the molecular mechanics framework using an effective dielectric constant of 80. The conformational space was thoroughly sampled using an iterative simulated annealing protocol. The bioactive conformation was assessed by pairwise cross comparisons of each of the unique low energy conformations found for each of the different analogs studied. After a putative bioactive conformation was selected, in order to further validate our hypothesis the conformational profile of the potent compound cyclo(Thr-Thr-Asn-Tyr-Thr-Asp) was computed and the putative bioactive conformation was found. The conformation exhibits a pseudo β-turn involving the side chain of Thr5 and the carbonyl oxygen of Tyr7 forming a C12 ring.

[1]  G M Crippen,et al.  Size‐independent comparison of protein three‐dimensional structures , 1995, Proteins.

[2]  A. Motta,et al.  Conformational analysis of peptide T and of its C‐pentapeptide fragment , 1989, Biopolymers.

[3]  U. Singh,et al.  A NEW FORCE FIELD FOR MOLECULAR MECHANICAL SIMULATION OF NUCLEIC ACIDS AND PROTEINS , 1984 .

[4]  C. Pert,et al.  PEPTIDE T IN TREATMENT OF AIDS , 1987, The Lancet.

[5]  C. Pert,et al.  CD4 receptor binding peptides that block HIV infectivity cause human monocyte chemotaxis , 1987, FEBS letters.

[6]  S. Salvadori,et al.  Synthesis, metabolic stability and chemotactic activity of peptide T and its analogues. , 2009, International journal of peptide and protein research.

[7]  R. Seyer,et al.  Synthesis of a biotinylated, iodinatable, and photoactivatable probe for angiotensin receptors. , 2009, International journal of peptide and protein research.

[8]  S. Salvadori,et al.  Structure-activity relationships of cyclic and linear peptide T analogues. , 2009, International journal of peptide and protein research.

[9]  A. Motta,et al.  A 500 MHz study of peptide T in a DMSO solution , 1988, FEBS letters.

[10]  J. Hénichart,et al.  Conformational study of the threonine-rich C-terminal pentapeptide of peptide T. , 1990, Biochemical and biophysical research communications.

[11]  S. Salvadori,et al.  A cyclic peptide T analogue with high chemotactic activity , 1992 .

[12]  G. Nikiforovich.  Computational molecular modeling in peptide drug design. , 2009, International journal of peptide and protein research.

[13]  E. Farber,et al.  Peptide T improves psoriasis when infused into lesions in nanogram amounts. , 1991, Journal of the American Academy of Dermatology.