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Multivalent protein-protein interactions including bivalent and trivalent interactions play a critical role in mediating a wide range of biological processes. Hence, there is a significant interest in developing molecules that can modulate those signaling pathways mediated by multivalent interactions. For example, multimeric molecules capable of binding to a receptor protein through a multivalent interaction could serve as modulators of such interactions. However, it is challenging to efficiently generate such multimeric ligands. Here, we have developed a facile solid-phase method that allows for the rapid generation of (homo- and hetero-) dimeric and trimeric protein ligands. The feasibility of this strategy was demonstrated by efficiently synthesizing fluorescently-labeled dimeric peptide ligands, which led to dramatically increased binding affinities (~400-fold improvement) relative to a monomeric 14-3-3σ protein ligand.
This article was published in the following journal.
Name: Bioorganic chemistry
Taking inspiration from the assembly of so-called peptoids (N-alkylglycine oligomers) we present a new synthetic methodology whereby N-heterocyclic carbene (NHC) based Pd ligands were assembled using ...
We investigated the ultrasonication-mediated effects on the Fmoc-based solid-phase peptide synthesis (SPPS). Our study culminated with the development of an ultrasound-assisted strategy (US-SPPS) that...
Quasi phase-pure (>98 wt %) MAX phase solid solution ceramics with the (Zr,Ti)(Al,Sn)C stoichiometry and variable Zr/Ti ratios were synthesized by both reactive hot pressing and pressureless sintering...
The aim of this work was to develop an efficient method for the selective extraction and analysis of fenoxycarb, a carbamate pesticide, in mussel samples using a molecularly imprinted solid phase extr...
Carbon-14 ( C) labelled active pharmaceutical ingredients (APIs) and investigational medicinal products (IMPs) are required for Phase 0/I to Phase III mass balance and micro-dosing clinical trials. In...
A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) or Its Ligands
This is an open-label, Phase 1, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficac...
The investigators hypothesize that the CXCR2 ligands/CXCR2 biological axis plays an important role in promoting angiogenesis in PC; and that the genetic changes and the microenvironment of...
CA-170 is a rationally designed and orally available, small molecule that directly targets the Programmed death-ligands 1 and 2 (PD-L1/PD-L2), and V-domain Ig suppressor of T cell activati...
This is a single-centre, single arm, open-label pilot study to evaluate the safety and feasibility of CAR-NK cell treatment in subjects with metastatic solid tumours. Autologous or allogen...
Prospective Observational Study to Investigate the Added Value of the Health Related Quality of Life and Patient Reported Symptoms in the Identification of the Recommended Phase II Dose in Phase I Trials of Molecularly Targeted Therapies.
A prospective cohort of 250 patients with solid tumours included in phase I clinical trials of targeted agents will be enrolled. Patients will be treated with MTA in mono therapy or in ass...
An extraction method that separates analytes using a solid phase and a liquid phase. It is used for preparative sample cleanup before analysis by CHROMATOGRAPHY and other analytical methods.
Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix.
Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.
A solventless sample preparation method, invented in 1989, that uses a fused silica fiber which is coated with a stationary phase. It is used for sample cleanup before using other analytical methods.
Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (AEROSOLS) and other colloidal systems; water-insoluble drugs may be given as suspensions.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...