TY - JOUR
T1 - Synthetic Fab fragments that bind the HIV-1 gp41 heptad repeat regions
AU - Liu, Yanyun
AU - Regula, Lauren K.
AU - Stewart, Alex
AU - Lai, Jonathan R.
N1 - Funding Information:
This work was funded by the Albert Einstein College of Medicine, the Einstein-Montefiore center for AIDS Research, the Arnold and Mabel Young Investigators Program, and the National Institutes of Health (R01-AI090249). A.S. was supported in part by a fellowship from the UNCF/Merck Science Initiative. We thank Sachdev Sidhu (University of Toronto) for helpful discussions, and Gustavo Da Silva for assistance with the D5 scFv purification.
PY - 2011/10/7
Y1 - 2011/10/7
N2 - Recent work has demonstrated that antibody phage display libraries containing restricted diversity in the complementarity determining regions (CDRs) can be used to target a wide variety of antigens with high affinity and specificity. In the most extreme case, antibodies whose combining sites are comprised of only two residues - tyrosine and serine - have been identified against several protein antigens. [F.A. Fellouse, B. Li, D.M. Compaan, A.A. Peden, S.G. Hymowitz, S.S. Sidhu, J. Mol. Biol. 348 (2005) 1153-1162.] Here, we report the isolation and characterization of antigen-binding fragments (Fabs) from such " minimalist" diversity synthetic antibody libraries that bind the heptad repeat regions of human immunodeficiency virus type 1 (HIV-1) gp41. We show that these Fabs are highly specific for the HIV-1 epitope and comparable in affinity to a single chain variable fragment (scFv) derived from a natural antibody repertoire that targets the same region. Since the heptad repeat regions of HIV-1 gp41 are required for viral entry, these Fabs have potential for use in therapeutic, research, or diagnostic applications.
AB - Recent work has demonstrated that antibody phage display libraries containing restricted diversity in the complementarity determining regions (CDRs) can be used to target a wide variety of antigens with high affinity and specificity. In the most extreme case, antibodies whose combining sites are comprised of only two residues - tyrosine and serine - have been identified against several protein antigens. [F.A. Fellouse, B. Li, D.M. Compaan, A.A. Peden, S.G. Hymowitz, S.S. Sidhu, J. Mol. Biol. 348 (2005) 1153-1162.] Here, we report the isolation and characterization of antigen-binding fragments (Fabs) from such " minimalist" diversity synthetic antibody libraries that bind the heptad repeat regions of human immunodeficiency virus type 1 (HIV-1) gp41. We show that these Fabs are highly specific for the HIV-1 epitope and comparable in affinity to a single chain variable fragment (scFv) derived from a natural antibody repertoire that targets the same region. Since the heptad repeat regions of HIV-1 gp41 are required for viral entry, these Fabs have potential for use in therapeutic, research, or diagnostic applications.
KW - Antibody engineering
KW - HIV-1
KW - Phage display
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U2 - 10.1016/j.bbrc.2011.09.012
DO - 10.1016/j.bbrc.2011.09.012
M3 - Article
C2 - 21925149
AN - SCOPUS:80053596391
SN - 0006-291X
VL - 413
SP - 611
EP - 615
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -
