ANTIBODY AND PEPTIDE BIOCONJUGATES
We leverage bioconjugation and chemoenzymatic techniques to study and manipulate biological systems, enabling the development of targeted drug delivery strategies.
ACS INFECTIOUS DISEASES 2023
Development of Host-Cleavable Antibody–Bactericide Conjugates against Extracellular Pathogens
This work details an antibody bactericide conjugate (ABC) design wherein BDT-4G, a lab-designed antimicrobial, is coupled to an anti-P. aeruginosa monoclonal antibody via a host-cleavable peptide linker. Following ABC binding to the bacterial cell surface, we demonstrate that host proteases cleave the peptide linker, and the released antimicrobial payload exhibits bactericidal activity.
against extracellular P. aeruginosa.
SCIENCE 2021
Intranasal fusion inhibitory lipopeptide prevents direct contact SARS-CoV-2 transmission in ferrets
We designed lipopeptide fusion inhibitors to block the critical first step of viral infection. Based on their in vitro efficacy and in vivo biodistribution, we selected a dimeric form for evaluation in an animal model. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 transmission through direct contact during 24-hour cohousing with infected animals.
CELL CHEMICAL BIOLOGY 2019
Responsive Antibody Conjugates Enable Quantitative Determination of Intracellular Bond Degradation Rate
Intracellular bond cleavage was visualized with a trastuzumab FRET probe via live-cell confocal microscopy and measured kinetically with flow cytometry. Fitting this kinetic data to a mass-action kinetics model quantified the rate constant of intracellular disulfide bond degradation in the HER2 pathway.
BIOCONJUGATE CHEMISTRY 2018
Substrate Design Enables Heterobifunctional, Dual “Click” Antibody Modification via Microbial Transglutaminase
We report a novel Fc-specific antibody bioconjugation method using a trifunctional linker equipped with two orthogonal reactive groups. This innovative synthetic approach employs orthogonal "click" conjugations to facilitate the one-pot assembly of a multifunctional Her2 antibody-drug conjugate. The conjugate incorporates a maytansine-derived cytotoxic payload and a hydrophobicity-masking PEG side chain. The resulting bifunctional antibody conjugate demonstrates significant Her2-specific cytotoxicity in vitro.