AHNP-streptavidin: a tetrameric bacterially produced antibody surrogate fusion protein against p185her2/neu.
The anti-p185(her2/neu) peptidomimetic (AHNP) is a small exo-cyclic peptide derived from the anti-p185(her2/neu) rhumAb 4D5 (h4D5). AHNP mimics many but not all of the antitumor characteristics exhibited by h4D5. However, the pharmacokinetic profiles of AHNP are less than optimal for therapeutic or diagnostic purposes. To improve the binding affinity to p185(her2/neu) and the antitumor efficacy, we have engineered a fusion protein containing AHNP and a nonimmunoglobulin protein scaffold, streptavidin (SA). The recombinant protein, AHNP-SA (ASA) bound to p185(her2/neu) with high affinity, inhibited the proliferation of p185(her2/neu)-overexpressing cells, and reduced tumor growth induced by p185(her2/neu)-transformed cells. These data suggest that the bacterially produced tetrameric ASA can be used as an antibody-surrogate molecule. This class of molecule will play a role in the diagnosis and treatment of p185(her2/neu)-related tumors. Our studies establish a general principle by which a small biologically active synthetic exo-cyclic peptide can be engineered to enhance functional aspects by structured oligomerization and can be produced recombinantly using bacterial expression.
Masuda
K
K
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
Richter
M
M
Song
X
X
Berezov
A
A
Masuda
K
K
Murali
R
R
Greene
M I
MI
Zhang
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental / Q000188:drug therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D019809:Streptavidin / Q000096:biosynthesis* / Q000737:chemistry
D000911:Antibodies, Monoclonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D019809:Streptavidin; C404542:anti-HER2-neu peptide mimic, 1.5 kDa