Antibody like peptidomimetics as large scale immunodetection probes.
Antibodies are often used to study the molecular basis of physiologic processes. Despite the widespread applications of monoclonal antibodies (mAb) from basic science to successful therapeutics in clinical settings their use is limited. Production of mAb is often cumbersome and creating diverse and therapeutic amounts of useful mAb is difficult. We have developed a methodology to reduce an antibody into much smaller peptidomimetics and have engineered the mimetics for increased serum half life and affinity. The novel species are termed "antibody like binding peptidomimetics" (ABiP). We developed the Anti-Her2/neu peptidomimetic (AHNP) which is a mimic of Herceptin, a mAb used for advanced breast cancer therapy. The AHNP has been used as a defining tool to develop immunodetection probes that exemplify a general process application. AHNP has been expressed as an oligomeric fusion protein with streptavidin. These Herceptin like ABiPs were used to detect the Her2/neu antigen at extremely low concentrations using the immunodetection amplification technique (IDAT) which our laboratory has also developed. A fully developed highly diverse library of ABiPs represents an alternative for panels of monoclonal antibodies and may also be useful for target validation, antigen detection, therapeutics and as a platform for drug development.
Murali
R
R
252 John Morgan Building, Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research, University of Pennsylvania, 36th and Hamilton Walk, Philadelphia, PA 19104-6082, USA.
Liu
Q
Q
Cheng
X
X
Berezov
A
A
Richter
M
M
Furuchi
K
K
Greene
M I
MI
Zhang
H
H
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D006801:Humans; D015336:Molecular Probe Techniques; D015335:Molecular Probes; D010455:Peptides / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D014764:Viral Proteins
D000906:Antibodies; D012321:DNA-Directed RNA Polymerases; D015335:Molecular Probes; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D014764:Viral Proteins; C062210:bacteriophage T7 RNA polymerase