Author's posts
Jun 04 2021
Inhibition of Cancer Cell Adhesion, Migration and Proliferation by a Bispecific Antibody that Targets two Distinct Epitopes on αv Integrins
Gallo E, Kelil A, Haughey M, Cazares-Olivera M, Yates BP, Zhang M, Wang NY, Blazer L, Carderelli L, Adams JJ, Kossiakoff AA, Wells JA, Xie W, Sidhu SS
J Mol Biol. 2021 Jun 4;433(15):167090. doi: 10.1016/j.jmb.2021.167090.
PMID: 34090922
Members of the αv family of integrins regulate activation of transforming growth factor beta (TGFβ) and are …
Mar 25 2021
Engineered ultra-high affinity synthetic antibodies for SARS-CoV-2 neutralization and detection
Slezak T, Kossiakoff AA
J Mol Biol. 2021 Mar 25;doi: 10.1016/j.jmb.2021.166956.
PMID: 33775667
Abstract
The Covid-19 pandemic is a centenarial global catastrophe. Similar events are likely to be recurring with more frequency in the future. The inability to control the virus’ impact is caused by many factors, but the lack of a technology infrastructure to …
Sep 01 2020
Recognition of an α-helical hairpin in P22 large terminase by a synthetic antibody fragment
Lokareddy RK, Ko YH, Hong N, Doll SG, Paduch M, Niederweis M, Kossiakoff AA, Cingolani G
Acta Crystallogr D Struct Biol. 2020 Sep 1;76(Pt 9):876-888.
PMID: 32876063
Abstract
The genome-packaging motor of tailed bacteriophages and herpesviruses is a multisubunit protein complex formed by several copies of a large (TerL) and a small (TerS) terminase subunit. …
Aug 07 2020
Structure of human Frizzled5 by fiducial-assisted cryo-EM supports a heterodimeric mechanism of canonical Wnt signaling
Tsutsumi N, Mukherjee S, Waghray D, Janda CY, Jude KM, Miao Y, Burg JS, Aduri NG, Kossiakoff AA, Gati C, Garcia KC.
Elife. 2020 Aug 7;9:e58464.
PMID: 32762848
Abstract
Frizzleds (Fzd) are the primary receptors for Wnt morphogens, which are essential regulators of stem cell biology, yet the structural basis of Wnt signaling through Fzd remains …
Jan 29 2018
Automated antibody phage display selection and screening system
Advanced robotic system designed to screen thousands of recombinant antibodies without human intervention.
Jan 10 2018
Engineered synthetic antibodies as probes to quantify the energetic contributions of ligand binding to conformational changes in proteins
Mukherjee S, Griffin DH, Horn JR, Rizk SS, Nocula-Lugowska M, Malmqvist M, Kim SS, Kossiakoff AA
J. Biol. Chem. 2018 Feb;293(8):2815-2828
PMID: 29321208
Abstract
Conformational changes in proteins due to ligand binding are ubiquitous in biological processes and are integral to many biological systems. However, it is often challenging to link ligand-induced conformational changes to …
Apr 03 2017
Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody
Rizk SS, Mukherjee S, Koide A, Koide S, Kossiakoff AA
Sci Rep 2017 Apr;7(1):556
PMID: 28373671
Abstract
We have utilized a high-diversity phage display library to engineer antibody fragments (Fabs) that can modulate the activity of the enzyme isocitrate dehydrogenase 1 (IDH1). We show that a conformation-specific Fab can reactivate an IDH1 mutant associated with …
Mar 03 2017
Generating Conformation and Complex-Specific Synthetic Antibodies
Paduch M, Kossiakoff AA
Methods Mol. Biol. 2017;1575:93-119
PMID: 28255876
Abstract
Phage display is commonly used to identify and isolate binders from large combinatorial libraries. Here we present phage selection protocols enabling generation of synthetic antibodies capable of recognizing multiprotein complexes and conformational states. The procedure describes stages of the experiment design, optimization, and screening, …
Mar 01 2017
Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity
Sundaram KM, Zhang Y, Mitra AK, Kouadio JK, Gwin K, Kossiakoff AA, Roman BB, Lengyel E, Piccirilli JA
Cancer Res. 2017 Apr;77(7):1684-1696
PMID: 28202518
Abstract
Poor prognosis of ovarian cancer, the deadliest of the gynecologic malignancies, reflects major limitations associated with detection and diagnosis. Current methods lack high sensitivity to detect small tumors and high …
Feb 26 2017
Generation of Synthetic Antibody Fragments to Detergent Solubilized Membrane Proteins
Uysal S, Kossiakoff AA
Springer Protocols Handbook, p1-13
Abstract
Structural determination of membrane proteins is extremely challenging due to the physical characteristics of membrane proteins themselves and the lack of adequate tools and technologies to perform the studies. Recent developments in micro-focus X-ray beams, novel detergents, protein thermo-stabilization, and protein engineering have been essential in …