Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight.

Polyanhydrides have been synthesized for decades by melt-polycondensation of diacid monomers and 5 to >10 times mole excess acetic anhydride to diacid monomers to form polymers with a polydispersity ranging from 2.5 to 6 and low reproducibility. Hydrophobic segments in polyanhydrides are beneficial to hinder the characteristic hydrolytic cleavage of an anhydride bond that provides stable polyanhydrides at room temperature.

Characterization and Evaluation of Injectable Biodegradable Polymer Multimodality Radiologic Markers in an In Vivo Murine Model.

Biodegradable polymer clips as multidimensional soft tissue biopsy markers were developed with better biocompatibility and imaging features. Unlike the commercially available metallic biopsy markers, the developed polymer clips are temporary implants with similar efficacies as metal markers in imaging and detection and get absorbed within the body with time. Herein, we evaluate the degradation rate of three resorbable polymer-based marker compounds in an in vivo murine model.

Seven Post-synthetic Covalent Reactions in Tandem Leading to Enzyme-like Complexity within Metal-Organic Framework Crystals.

The design of enzyme-like complexity within metal-organic frameworks (MOFs) requires multiple reactions to be performed on a MOF crystal without losing access to its interior. Here, we show that seven post-synthetic reactions can be successfully achieved within the pores of a multivariate MOF, MTV-IRMOF-74-III, to covalently incorporate tripeptides that resemble the active sites of enzymes in their spatial arrangement and compositional heterogeneity. These reactions build up H2N-Pro-Gly-Ala-CONHL and H2N-Cys-His-Asp-CONHL (where L = organic struts) amino acid sequences by covalently attaching them to the organic struts in the MOFs, without losing porosity or crystallinity.

L-Aspartate links for stable sodium metal-organic frameworks.

Metal-organic frameworks (MOFs) based purely on sodium are rare, typically due to large numbers of coordinating solvent ligands. We designed a tetratopic aspartate-based linker with flexible carboxylate groups to enhance framework stability. We report two new air-stable sodium MOFs, MOF-705 and MOF-706, comprising 2D sodium oxide sheets.

Extended ubiquitin species are protein-based DUB inhibitors.

A frameshift mutation in the transcript of the ubiquitin-B gene leads to a C-terminally extended ubiquitin (Ub), UBB(+1). UBB(+1) has been considered to inhibit proteasomes and as such to be the underlying cause for toxic protein buildup correlated with certain neuropathological conditions. We demonstrate that expression of extended Ub variants leads to accumulation of heterogeneously linked polyubiquitin conjugates, indicating a pervasive effect on Ub-dependent turnover.

Systematic identification of proteins binding to chromatin-embedded ubiquitylated H2B reveals recruitment of SWI/SNF to regulate transcription.

Chromatin posttranslational modifications (PTMs), including monoubiquitylation of histone H2B on lysine 120 (H2Bub1), play a major role in regulating genome functions. To elucidate the molecular mechanisms of H2Bub1 activity, a chromatin template uniformly containing H2Bub1 was used as an affinity matrix to identify preferentially interacting human proteins. Over 90 such factors were found, including proteins and protein complexes associated with transcription, RNA posttranscriptional modifications, and DNA replication and repair.

Chemical and semisynthesis of posttranslationally modified proteins.

Posttranslational modifications of proteins play crucial roles in health and disease by affecting numerous aspects of protein structure, function, stability and sub cellular localization. Yet understanding the effects of these modifications on several of these processes at the molecular level has been hindered by the lack of homogeneously modified proteins obtained via traditional biochemical and molecular biology approaches. Moreover, the preparation of such bioconjugates at a workable level is highly demanding.

Native chemical ligation at glutamine.

The desulfurization reaction introduced by Yan and Dawson as a postnative chemical ligation step greatly expanded the scope of ligation chemistry beyond Xaa-Cys (Xaa is any amino acid) by making ligation at Xaa-Phe, Xaa-Val, Xaa-Lys, Xaa-Leu, Xaa-Thr, and Xaa-Pro junctions accessible in the synthesis of functional proteins. A new ligation site based on Xaa-Gln utilizing γ-mercaptoglutamine is reported, and several examples on the efficiency of ligation coupled with desulfurization are provided.

Chemical synthesis and expression of the HIV-1 Rev protein.

The HIV-1 Rev protein is responsible for shuttling partially spliced and unspliced viral mRNA out of the nucleus. This is a crucial step in the HIV-1 lifecycle, thus making Rev an attractive target for the design of anti-HIV drugs. Despite its importance, there is a lack of structural, biophysical, and quantitative information about Rev.