Peptides - Latest research and news (2024)

Elastin-like polypeptide coacervates as reversibly triggerable compartments for synthetic cells

Compartmentalization within living cells is vital to orchestrate intracellular processes, but effective compartmentalization and organization within synthetic cells remains a key challenge. Here, the authors report a lab-on-a-chip system to reversibly trigger the formation of peptide-based coacervates as membraneless organelles via pH/temperature/osmolyte variations within cell-mimicking confinements.

• Chang Chen
• Ketan A. Ganar
• Siddharth Deshpande

Hydrogen bonding patterns and cooperativity in polyproline II helical bundles

Hydrogen bond cooperativity (HBC) plays an important role in the stability of protein assemblies built by α-helices and β-sheets, however, it remains unknown whether HBC also exists in polyproline II (PPII) helices. Here, the authors show that HBC stabilizes intermolecular PPII helices using computational chemistry tools and molecular modeling corroborated by experimental observations.

• Rubén López-Sánchez
• Douglas V. Laurents
• Miguel Mompeán

Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors

Qiao and Nguyen et al. describe a strategy to block hypoxia-dependent gene expression in cell and mouse models of breast cancer through dual targeting of X-box-binding protein 1 and hypoxia-inducible factor binding to DNA with fully synthetic, stabilized artificial transcription factors.

• Zeyu Qiao
• Long C. Nguyen
• Raymond E. Moellering

A Foundation Model Identifies Broad-Spectrum Antimicrobial Peptides against Drug-Resistant Bacterial Infection

New approaches to develop antimicrobial agents are urgently needed. In this study, the authors develop a peptide language-based deep generative model to design broad-spectrum antimicrobial peptides against drug-resistant bacteria and validate promising candidates in a wound mouse model.

• Tingting Li
• Xuanbai Ren
• Feixiong Cheng

Proximity-driven site-specific cyclization of phage-displayed peptides

Cyclization provides a general strategy for improving peptide proteolytic stability, cell membrane permeability and target binding affinity. Here the authors develop a cyclopropenone-based proximity-driven chemical linker for the site-specific cyclization of phage-displayed peptides.

• Libby Brown
• Aldrin V. Vidal
• Gonçalo J. L. Bernardes

Polyphenol-stabilized coacervates for enzyme-triggered drug delivery

Membrane-free coacervates are interesting, but balancing stability and permeability can be challenging. Here, the authors report the use of a tannic acid modification to improve stability, and subsequent use of the modified coacervates in enzyme-triggered drug release.

• Wonjun Yim
• Zhicheng Jin
• Jesse V. Jokerst

Enzymatic synthesis of peptide therapeutics

Peptides are fundamental in life and are widely used as therapeutic agents; however, they are problematic to produce by chemical synthesis. The discovery of unusual biosynthetic pathways that produce peptide natural products reveals an alternative approach for peptide synthesis that uses ‘standalone’ ligase enzymes rather than multimodular enzymes.

Antibody–peptide conjugates for targeted inhibition of cysteine proteases

We developed a rational approach to design peptide-based covalent inhibitors and coupled the inhibitors with antibodies for cell-specific delivery. We used this platform to generate antibody–peptide inhibitor conjugates (APICs) that target a family of proteases, the cysteine cathepsins. Our drug design and targeted delivery approach ensure specific inhibition and achieve therapeutic efficacy in different cancer cells and osteoclasts.

PROTAC-ing tuberculosis

Targeted protein degradation has emerged as a promising approach in drug discovery, harnessing a cell’s intrinsic machinery to eliminate disease-related proteins. Now, a study paves the way to translating this technology into potential anti-mycobacterial therapies, by exploiting the bacterial protein-degradation complex.

• Delia Preti
• Valentina Albanese
• Peggy Carla Raffaella Marconi

Another side of side chains

Peptide stapling has traditionally relied on the incorporation of unnatural amino acids and symmetric stapling. A recent article targets a typically inert C–H bond within the serine side chain, offering new avenues for conformational control and side chain engineering.

• Fa-Jie Chen

A peptide dehydratase with core strength

Ribosomally synthesized and post-translationally modified peptide (RiPP) natural products typically rely on substrate recognition through remote protein–protein interaction sites. Now, an atypical dehydratase, whose activity is directed by neighboring azole modifications, has been shown to produce a highly modified peptide hybrid bearing dehydroamino acids, enabling the synthesis of members of the dehydrazole family of RiPPs.

• Daniel Richter
• Anna Lisa Vagstad

Peptide vaccines get an OS update

Peptide vaccines use antigenic peptide fragments to induce an immune response but are problematic because of the short half-life of peptides. A study now reports thioamide substitution in the peptide backbone as a strategy to enhance resistance to proteolysis and promote binding to the MHC I complex for T cell activation.

• Martin Zacharias
• Sebastian Springer