87184-24-5Relevant academic research and scientific papers
Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity
Wei, Binqing,Gunzner-Toste, Janet,Yao, Hui,Wang, Tao,Wang, Jing,Xu, Zijin,Chen, Jinhua,Wai, John,Nonomiya, Jim,Tsai, Siao Ping,Chuh, Josefa,Kozak, Katherine R.,Liu, Yichin,Yu, Shang-Fan,Lau, Jeff,Li, Guangmin,Phillips, Gail D.,Leipold, Doug,Kamath, Amrita,Su, Dian,Xu, Keyang,Eigenbrot, Charles,Steinbacher, Stefan,Ohri, Rachana,Raab, Helga,Staben, Leanna R.,Zhao, Guiling,Flygare, John A.,Pillow, Thomas H.,Verma, Vishal,Masterson, Luke A.,Howard, Philip W.,Safina, Brian
supporting information, p. 989 - 1000 (2018/01/01)
Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.
PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF
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Page/Page column 146, (2015/07/07)
This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.
Transport of antimicrobial agents using peptide carrier systems: Anticandidal activity of m-fluorophenylalanine-peptide conjugates
Kingsbury,Boehm,Mehta,Grappel
, p. 1725 - 1729 (2007/10/02)
A series of di- and tripeptides containing D- and L-m-fluorophenylalanine was prepared and tested in vitro for the ability to inhibit the growth of the yeast Candida albicans. The results demonstrate that peptides containing L-m-fluorophenylalanine inhibi
