Designing of peptides with immuno-modulatory properties using protein A as a probe.
A series of reports from our laboratory have described the multifarious properties of protein A of Staphylococcus aureus Cowan I, apart from its IgG binding affinity. Original reports regarding its anti-tumor, anti-toxic, anti-carcinogenic and immunomodulatory properties published earlier by the authors have implicated some uniqueness of this bacterial protein. It was conceived that such diversified properties must lie in its specific peptide sequences, rendering it to act and behave as a multipotent "Biological Response Modifier" (BRM). The high resolution X-ray structure of protein A-Fc complex has been delineated earlier, and has been the foundation of many protein engineering studies. This structure along with the amino acid sequence data of its four repetitive domains provided us the basis for designing an octapeptide. This octapeptide was synthesized by solid phase peptide synthesis considering it as the probable site through which PA binds IgG. This octapeptide (NH2-Gln-Asn-Ala-Phe-Tyr-Glu-Ile-Leu-COOH) is present in the first helical segment of B-domain of protein A, and also is a part of domain D, A and C. This octapeptide has been shown to bind IgG by the immunoblotting technique. The binding affinity of the octapeptide appears to be significantly higher than that of intact protein A, as was revealed by calculation of Ka (association constant) and Kd (dissociation constant) values. This octapeptide might serve as a good immunoadsorbant for IgG and/or immune complexes.
Ray
P K
PK
Immunotechnology Section & Distributive Information Centre, Bose Institute, Calcutta.
Datta
P K
PK
Modak
D P
DP
Mandal
C
C
Rao
N S
NS
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D015195:Drug Design; D015335:Molecular Probes; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D013205:Staphylococcal Protein A
D000276:Adjuvants, Immunologic; D015335:Molecular Probes; D010455:Peptides; D013205:Staphylococcal Protein A