Cell penetration and nucleus translocation efficiency are important for the cellular activities of peptide therapeutics. For helical peptides stabilized by N-terminal crosslinked aspartic acid, correlations between their penetration efficiency/nucleus translocation and physicochemical properties were studied. An increase in hydrophobicity...

Direct inhibition of the protein−protein interaction of ERα and its endogenous coactivators with a cell permeable stabilized peptide may offer a novel, promising strategy for combating ERα positive breast cancers. Here, we report the cocrystal structure of a helical...

Li group published article on Theranostics about a study of siRNA delivery with PEGylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer.   Since the successful exfoliation of graphene from graphite in 2004, graphene and graphene...

Link: http://www.thno.org/v07p4566.pdf Abstract: Inhibition of the interaction between p53 and MDM2/MDMX has attracted significant attention in anticancer therapy development. We designed a series of in-tether chiral center-induced helical stabilized peptides, among which MeR/PhR effectively reactivated p53. The activation of p53...

The addition of a precisely positioned chiral center in the tether of a constrained peptide is reported, yielding two separable peptide diastereomers with significantly different helicity, as supported by circular dichroism (CD) and NMR spectroscopy. Single crystal X-ray diffraction analysis suggests that the...

Recently, we developed methods to stabilize peptides into various secondary structures, including a-helix, type III turn and b-hairpin via proper thioether based macrocyclization. These conformationally constrained peptidomimetics confer enhanced biophysical properties and provide a valuable avenue towards clinically-relevant therapeutic...

The preS antigen of hepatitis B virus (HBV) corresponds to the N-terminal polypeptide in the large (L) antigen in addition to the small (S) antigen. The virus-like particle (VLP) of the S antigen is widely used as a vaccine...

Peptide stapling emerged as a versatile strategy to recapitulate the bioactive helical conformation of unstructured short peptides in water to improve their therapeutic properties in targeting intracellular “undruggable” targets. Here, we describe the development of photo-induced intramolecular thiol–yne macrocyclization...

Recapitulation of well-defined α-helices could result in constrained peptide mimetics with preferable secondary structures and enhanced therapeutic properties for various purposes. Among the helix-stabilizing strategies, the nucleation strategies are able to maximize recognition specificity of the original sequence without...

Peptide modulators targeting protein-protein interactions (PPIs) exhibit greater potential than small-molecule drugs in several important aspects including facile modification and relative large contact surface area. Stabilized peptides constructed by variable chemistry methods exhibit improved peptide stability and cell permeability...

Li group published article on Nano Research about a study of A simple and novel method for the quantitative detection of 5-hydroxymethylcytosine using carbon nanotube field- effect transistors.   5-hydroxymethylcytosine (5-hmC) is an important epigenetic derivative of cytosine and quantitative...

A lipid–cell-penetrating-peptide (CPP) conjugate was designed to deliver cargoes with poor cellular permeability, including peptides or small-molecule therapeutics, into cells. The lipid–CPP conjugate facilitated the cellular uptake of cargoes noncovalently through an ATP-dependent micropinocytosis mechanism. This delivery system is...

The N-methylation effects on CIH peptides’ biophysical properties were systematically studied. The N-methylation at the N terminal NH could help improve the peptides’ cellular uptakes with retained helical conformation. This Nmethylation strategy could also be applied to longer peptides...

Li group published article on Chembiochem. about a study of A Thioether-Stabilized d-Proline–l-Proline-Induced β-Hairpin Peptide of Defensin Segment Increases Its Anti-Candida albicans Ability   We report a β-hairpin dual stabilizing strategy: a d-proline-l-proline (d-Pro-l-Pro) dipeptide as the nucleating turn,...

The facile chemical modification on the peptide cross-linking moiety is an important strategy to improve the physicochemical properties of a peptide. Herein, peptides were contrained into helical conformations via the synergistic effects of dual in-tether chiral centers. A pentapeptide...