Research into various proteins capable of blocking metabolic pathways has improved the detection and treatment of multiple pathologies associated with the malfunction and overexpression of different metabolites. However, antigen-binding proteins have limitations. To overcome the disadvantages of the available antigen-binding proteins, the present investigation aims to provide chimeric antigen-binding peptides by binding a complementarity-determining region 3 (CDR3) of variable domains of new antigen receptors (VNARs) with a conotoxin. Six non-natural antibodies (NoNaBodies) were obtained from the complexes of conotoxin cal14.1a with six CDR3s from the VNARs of and two NoNaBodies from the VNARs of other shark species. The peptides cal_P98Y vs. vascular endothelial growth factor 165 (VEGF), cal_T10 vs. transforming growth factor beta (TGF-β), and cal_CV043 vs. carcinoembryonic antigen (CEA) showed in-silico and in vitro recognition capacity. Likewise, cal_P98Y and cal_CV043 demonstrated the capacity to neutralize the antigens for which they were designed.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141372 | PMC |
http://dx.doi.org/10.3390/toxins15040269 | DOI Listing |
Bioorg Med Chem
January 2025
Dr. Ikram-ul-Haq Institute of Industrial Biotechnology, Government College University, Lahore 54000, Pakistan; Pakistan Academy of Sciences, Islamabad, Pakistan.
Antibody-drug conjugates (ADCs) represent a powerful class of targeted cancer therapies that harness the specificity of monoclonal antibodies to deliver cytotoxic payloads directly to tumor cells, minimizing off-target effects. This review explores the advancements in ADC technologies, focusing on advancing next-generation ADCs with novel payloads, conjugation strategies, and enhanced pharmacokinetic profiles. In particular, we highlight innovative payloads, including microtubule inhibitors, spliceosome modulators, and RNA polymerase inhibitors, that offer new mechanisms of cytotoxicity beyond traditional apoptosis induction.
View Article and Find Full Text PDFChem Rev
November 2024
University of Tokyo, Department of Chemistry, Graduate School of Science 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Technological advances and breakthrough developments in the pharmaceutical field are knocking at the door of the "undruggable" fortress with increasing insistence. Notably, the 21st century has seen the emergence of macrocyclic compounds, among which cyclic peptides are of particular interest. This new class of potential drug candidates occupies the vast chemical space between classic small-molecule drugs and larger protein-based therapeutics, such as antibodies.
View Article and Find Full Text PDFMAbs
October 2024
Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering, Swiss Federal Institute of Technology, Zurich, Switzerland.
Engineered antibody formats, such as antibody fragments and bispecifics, have the potential to offer improved therapeutic efficacy compared to traditional full-length monoclonal antibodies (mAbs). However, the translation of these non-natural molecules into successful therapeutics can be hampered by developability challenges. Here, we systematically analyzed 64 different antibody constructs targeting Tumor Necrosis Factor (TNF) which cover 8 distinct molecular format families, encompassing full-length antibodies, various types of single chain variable fragments, and bispecifics.
View Article and Find Full Text PDFPharmaceutics
September 2024
Instituto de Investigación Biosanitaria ibs.GRANADA, Avda de Madrid, 15, 18012 Granada, Spain.
Antibody drug conjugates are an exciting therapeutic modality that combines the targeting specificity of antibodies with potent cytotoxins to selectively kill cancer cells. The targeting component improves efficacy and protects non-target cells from the harmful effects of the payload. To date 15 ADCs have been approved by regulatory agencies for commercial use and shown to be valuable tools in the treatment of cancer.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!