Constrained peptide libraries as a tool for finding mimotopes.
The monoclonal antibody (mAb) KAA8 recognizes the peptide angiotensin II (AII). The KAA8 mAb was biopanned using two phage-displayed peptide libraries, one unconstrained, the other constrained by a disulfide bond. After several cycles of biopanning, both libraries showed enrichment for phage that bind KAA8. Phage isolated from the unconstrained library contain a consensus sequence that matches the sequence of AII. A consensus sequence was also identified from the constrained library that does not resemble the AII sequence, and represents a mimotope of AII. We have also demonstrated that monovalent phage display can be used to discriminate between modest and high-affinity binding peptides.
McConnell
S J
SJ
DuPont Merck Pharmaceutical Company, Experimental Station, Wilmington, DE 19980-0328.
Kendall
M L
ML
Reilly
T M
TM
Hoess
R H
RH
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D000911:Antibodies, Monoclonal; D003001:Cloning, Molecular; D003360:Cosmids; D015723:Gene Library; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D010455:Peptides; D000804:Angiotensin II