Structure-guided design of peptidic ligand for human prostate specific antigen.
Prostate specific antigen (PSA) is a member of kallikrein family having serine protease-like activity and acts as a prognostic marker of prostate carcinoma. Various studies have been performed on inhibition of PSA and such targeting requires the identification of highly selective peptide inhibitors. PSA was purified from human seminal plasma by rapid and efficient methods, and binding studies for various peptides were carried out by fluorescence spectroscopy and SPR. The 'S' of PSA is predominated by hydrophobic residues, and hence many hydrophobic peptides were used to determine their binding affinity to PSA by fluorescence spectroscopy. We observed that LLFW, FFKW, and KFW binds strongly to PSA, among them LLFW showed strong binding. SPR also showed strong binding affinity of PSA toward peptides with hydrophobic and basic residues. Among the peptides used, FWYS showed dramatic increase in binding affinity (10(-10) M). The peptides analyzed for binding studies, suggests that peptide with Trp residue along with basic or hydrophobic amino acids may be useful for designing specific inhibitors for PSA. The strong affinities of designed peptides for PSA can be a valuable tool for designing therapeutic agents for prostate carcinomas.
Hassan
Md Imtaiyaz
MI
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Kumar
Vijay
V
Somvanshi
Rishi K
RK
Dey
Sharmistha
S
Singh
Tej P
TP
Yadav
Savita
S
D001665:Binding Sites; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D010455:Peptides / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors* / Q000097:blood / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance / Q000379:methods; D013997:Time Factors
D008024:Ligands; D010455:Peptides; D017430:Prostate-Specific Antigen