Endosomolytic peptides enable the cellular delivery of peptide nucleic acids.

Precision genetic medicine enlists antisense oligonucleotides (ASOs) to bind to nucleic acid targets important for human disease. Peptide nucleic acids (PNAs) have many desirable attributes as ASOs but lack cellular permeability. Here, we use an assay based on the corrective splicing of an mRNA to assess the ability of synthetic peptides to deliver a functional PNA into a human cell.

An outcome-defining role for the triple-helical domain in regulating collagen-I assembly.

Collagens are the foundational component of diverse tissues, including skin, bone, cartilage, and basement membranes, and are the most abundant protein class in animals. The fibrillar collagens are large, complex, multidomain proteins, all containing the characteristic triple helix motif. The most prevalent collagens are heterotrimeric, meaning that cells express at least two distinctive procollagen polypeptides that must assemble into specific heterotrimer compositions.

Pauli Exclusion by n→π* Interactions: Implications for Paleobiology.

Proteins have evolved to function in an aqueous environment. Collagen, which provides the bodily scaffold for animals, has a special need to retain its integrity. This need was addressed early on, as intact collagen has been detected in dinosaur fossils, even though peptide bonds have a half-life of only ∼500 years in a neutral aqueous solution.

Sitetack: a deep learning model that improves PTM prediction by using known PTMs.

Motivation: Post-translational modifications (PTMs) increase the diversity of the proteome and are vital to organismal life and therapeutic strategies. Deep learning has been used to predict PTM locations. Still, limitations in datasets and their analyses compromise success.

Mammalian Esterase Activity: Implications for Peptide Prodrugs.

As a traceless, bioreversible modification, the esterification of carboxyl groups in peptides and proteins has the potential to increase their clinical utility. An impediment is the lack of strategies to quantify esterase-catalyzed hydrolysis rates for esters in esterified biologics. We have developed a continuous Förster resonance energy transfer (FRET) assay for esterase activity based on a peptidic substrate and a protease, Glu-C, that cleaves a glutamyl peptide bond only if the glutamyl side chain is a free acid.