Themed collection The Chemical Biology of Peptides

Chemical methods for protein site-specific ubiquitination are important for the understanding of Ub signaling.

This review details discovery strategies and established applications of peptide-small molecule hybrids, classified by the added functionality imparted by the small molecule component.

Since the first report on activatable CPPs (ACPPs) in 2004, various methods of activation have been developed. Here, we provide an overview of the different ACPP strategies known to date and summarize the benefits, drawbacks, and future directions.

Cyclotides are plant-derived cyclic peptides that have emerged as promising scaffold molecules for designing peptide-based therapeutics. Cyclotide engineering may lead to the development of novel ligands of G protein-coupled receptors with improved pharmacological properties.

In this review, we give a concise overview of the known biosynthetic princples of class III and IV lanthipeptide synthtases.

We report the development of AKAP derived, conformationally constrained peptides designed to probe AKAP-localized PKC. The lead peptides, CSTAD5 and CSTAD6 permeate cells, bind PKC, disrupt its scaffolding by AKAPs to inhibit its scaffolded activity.

A rationally designed stapled JAZ peptide selectively inhibited MYCs, master-regulators of the jasmonate signaling in Arabidopsis thaliana. It is proposed as a novel chemical tool for the analysis of MYC related jasmonate signaling.

The synthesis and thrombin inhibitory activity of eight homogeneously sulfated variants of the haemathrin proteins from tick saliva is described.

A small, inherently fluorescent macrocyclic peptide constrained with a bimane-linker is cell permeable, and binds the human sliding clamp protein, PCNA, in a 3₁₀-helical conformation with nanomolar affinity.

The significant improvement in the binding affinity of the stapled peptide to the PSD-95 GK domain is mostly contributed by the reduction in the entropy penalty of the stapled peptide due to the restriction in the α-helical structure by stapling in the free state.

SIRT3 is a mitochondrial lysine deacetylase enzyme, regulating the activity of numerous mitochondrial proteins. Here, we have designed inhibitors of this enzyme, which exhibit selective inhibition of SIRT3 in cells by specific organelle localizing.

Sirtuin 2 (SIRT2) is a protein deacylase enzyme that removes acetyl groups and longer chain acyl groups from post-translationally modified lysine residues. Here, we developed small peptide-based inhibitors of its activity in living cells in culture.

The helical enhancement of a short oligoalanine peptide scaffold in anionic membranes triggered the supramolecular assembly of a nanopore, which allowed the transport and release of proteins in the cytosol of cells and tissues.

β-Amino acid based peptidomimetics are attractive scaffolds for therapeutics design towards T2D. They prevent amyloid formation of hIAPP by forming non-fibrillar non-toxic aggregates.

We show for the first time that PD-1 is palmitoylated, identify DHHC9 as the predominant enzyme for its palmitoylation, and reveal the molecular mechanisms underlying its effects on PD-1 stability and functions. Importantly, we also designed PD1-PALM, a competitive inhibitor of PD-1 palmitoylation, and this first-in-class molecule may inspire the development of new checkpoint inhibitors.

A new helix-loop-helix peptide scaffold with dual ability to transport cargo across cancer cell membranes and disrupt mitochondrial membrane function.

Leveraging interface peptides in PD-L1 for PET imaging of PD-1, providing a new paradigm for radiotracer development.

Long-range stapling of two Asn-linked PEG oligomers via olefin metathesis substantially increases the conformational stability of the WW and SH3 domain tertiary structures and the GCN4 coiled-coil quaternary structure.