This Special Issue will celebrate the chemistry and biology of peptides, from synthesis, to structure and modifications, to biology and applications, and finally to degradation. Submit your manuscript...

Bitopic ligands that engage two distinct binding sites offer exciting opportunities for finely tuned control of G protein-coupled receptor signaling. This Primer explores a recent study in PLOS Biology that reports novel nanobody-small molecule conjugates and demonstrates their logic-gated activity at co-expressed receptor pairs with improved signaling profiles.

Bitopic ligands are comprised of a pharmacophore and a linked moiety that bind to separate sites. This study shows that G-protein coupled receptors (GPCRs) that bind small molecules can be potently ac...

Job #AJO30338, WDR-00054776 Assistant Professor - Chemistry and Chemical Biology, Cornell University (Ithaca, NY), Chemistry and Chemical Biology, Cornell University, Ithaca, New York, US

World-renowned experts will offer their insights during the fifth annual ND3P Symposium, set for June 25-26. The symposium will be virtual and highly interactive.

Models of Ab-antigen complexes can be used to understand interaction mechanisms and for improving affinity. This study evaluates the use of the protein structure prediction algorithm AlphaFold (AF) fo...

The ability to study proteins in their native cellular context is crucial to our understanding of biology. In this work, we report a technology for intracellular protein editing, drawing from split in...

Technologies to modulate induced proximity at the cell surface advance the manipulation of diverse biological responses.

Models of Ab-antigen complexes can be used to understand interaction mechanisms and to improve affinity. This study evaluates the use of the protein structure prediction algorithm AlphaFold (AF) for e...

Several methods have been used to label antibodies to facilitate visualization of cognate targets. Here, we leverage a new variety of conjugation chemistry, based on a crosslinking nanobody, to label...

In this work, the authors develop mirror-image monobodies (Mb) made of D-amino acids against the BCR::ABL1 SH2 domain with high binding affinities. The heterochiral Mb-SH2 structures reveal an unusual...

Broad discussion is needed to chart a path forward.

The Roswell Park Emerging Leaders in Cancer Research Seminar Series features lectures by outstanding junior scientists from around the country on a diverse range of cancer-focused topics. This include...

A triple orthogonal linker (T-Linker)-based programmable platform enables integration of therapeutic modules into multimodal targeting chimeras (Multi-TACs) for tumor-targeted co-engagement of different immune cells within the tumor-immune microenvironment.

Methods that enable the on-demand synthesis of biologically active molecules offer the potential for a high degree of control over the timing and context of target activation; however, such approaches often require extensive engineering to implement. Tools to restrict the localization of assembly also remain limited. Here we present a new approach for stimulus-induced ligand assembly that helps to address these challenges. This methodology relies on the high affinity and specificity recognition exhibited by antibody fragments (nanobodies, Nbs). By using Nbs that recognize short peptide epitopes to create semisynthetic conjugates, we develop a bioengineering platform termed peptide epitope dimerization (PED) in which the addition of heterodimeric peptide composed of two Nb epitopes stimulates the proximity-induced synthesis of a functional ligand for the parathyroid hormone receptor-1, a G protein-coupled receptor. We further demonstrate that high efficiency assembly can be achieved on the cell surface via Nb-based delivery of template. This approach opens the door for the on-demand generation of bioactive receptor ligands preferentially at a desired biological niche.

Methods that enable the on-demand synthesis of biologically active molecules offer the potential for a high degree of control over the timing and context of target activation; however, such approaches often require extensive engineering to implement. Tools to restrict the localization of assembly also remain limited. Here we present a new approach for stimulus-induced ligand assembly that helps to address these challenges. This methodology relies on the high affinity and specificity recognition exhibited by antibody fragments (nanobodies, Nbs). By using Nbs that recognize short peptide epitopes to create semisynthetic conjugates, we develop a bioengineering platform termed peptide epitope dimerization (PED) in which the addition of heterodimeric peptide composed of two Nb epitopes stimulates the proximity-induced synthesis of a functional ligand for the parathyroid hormone receptor-1, a G protein-coupled receptor. We further demonstrate that high efficiency assembly can be achieved on the cell surface via Nb-based delivery of template. This approach opens the door for the on-demand generation of bioactive receptor ligands preferentially at a desired biological niche.

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Peptide–receptor interactions play critical roles in a wide variety of physiological processes. Methods to link bioactive peptides covalently to unmodified receptors on the surfaces of living cells ar...

It is the Year of Camelids! The year 2024 was designated the United Nations International Year of Camelids. Camelid animals, including alpacas, camels,