Hexadienyloxycarbonyl (Hdoc) - a mild acid labile protecting group for amines

Hexadienyloxycarbonyl is an amine protecting group which can be cleaved with 1% TFA in CH2Cl2. It is stable to Pd(0) and basic conditions and is proposed as a useful alternative to the trityl and Bpoc protecting groups

Ion-extraction ladder sequencing from bead-based libraries

Ion-extraction mass spectrometry of ladders of mixtures of isotopically labeled compounds from single beads allows the unambiguous sequencing of bead-based peptides and offers significant advantages over traditional methods of library analysis

Quinuclidine derivatives binding to mucarinic M3 receptors

Preparation of quinuclidine salts for the treatment of diseases mediated by the muscarinic M3 receptor

Design and synthesis of a library of chemokine antagonists

A library of chemokine antagonists has been synthesized using a combination of solid and solution-phase chemistry. Structures of known chemokine antagonists were used to produce a pharmacophore which served to guide monomer selection. Several combinations of monomers have resulted in providing novel chemokine antagonists which in some cases display dual chemokine receptor antagonism

Quinuclidine derivatives binding to mucarinic M3 receptors

Preparation of quinuclidine salts for the treatment of diseases mediated by the muscarinic M3 receptor

The development of automated patch clamp assays for canonical transient receptor potential channels TRPC3, 6, and 7

The canonical transient receptor potential channel subfamily (TRPC3, TRPC6, and TRPC7) contains Ca2+ permeable non-selective cation channels that are widely expressed in a variety of tissues. There is increasing evidence implicating TRPC channels, particularly TRPC3 and 6, in physiological and pathophysiological processes, eliciting interest in these channels as novel drug targets. Electrophysiology remains a benchmark technique for measuring ion channel function and accurately determining the pharmacological effects of compounds. In this report we describe the development of TRPC inhibitor assays on 2 automated planar patch clamp platforms - the IonWorks® Quattro™ and QPatch® systems. To enable activation of TRPC channels by carbachol, Chinese Hamster Ovary-K1 cells stably expressing the muscarinic M3 receptor were transduced with human TRPC3, TRPC6, or TRPC7 using BacMam viruses. TRPC3, 6, and 7 currents could be recorded on both platforms. However, the design of each platform limits which assay parameters can be recorded. Due to its continuous recording capabilities, the QPatch can capture both the activation and decay of the response. However, the transient nature of TRPC channels, the inability to reactivate and the large variation in peak currents limits the ability to develop assays for compound screening. The IonWorks Quattro, due to its discontinuous sampling, did not fully capture the peak of TRPC currents. However, due to the ability of the IonWorks Quattro to record from 64 cells per well, the variation from well to well was sufficiently reduced allowing for the development of medium-throughput screening assays. © Copyright 2014, Mary Ann Liebert, Inc. 2014

Preparation of cyclic guanidinocarbonylpyrazines as epithelial sodium channel (ENaC) blockers

No description supplie

The development of automated patch clamp assays for canonical transient receptor potential channels TRPC3, 6, and 7

The canonical transient receptor potential channel subfamily (TRPC3, TRPC6, and TRPC7) contains Ca2+ permeable non-selective cation channels that are widely expressed in a variety of tissues. There is increasing evidence implicating TRPC channels, particularly TRPC3 and 6, in physiological and pathophysiological processes, eliciting interest in these channels as novel drug targets. Electrophysiology remains a benchmark technique for measuring ion channel function and accurately determining the pharmacological effects of compounds. In this report we describe the development of TRPC inhibitor assays on 2 automated planar patch clamp platforms - the IonWorks® Quattro™ and QPatch® systems. To enable activation of TRPC channels by carbachol, Chinese Hamster Ovary-K1 cells stably expressing the muscarinic M3 receptor were transduced with human TRPC3, TRPC6, or TRPC7 using BacMam viruses. TRPC3, 6, and 7 currents could be recorded on both platforms. However, the design of each platform limits which assay parameters can be recorded. Due to its continuous recording capabilities, the QPatch can capture both the activation and decay of the response. However, the transient nature of TRPC channels, the inability to reactivate and the large variation in peak currents limits the ability to develop assays for compound screening. The IonWorks Quattro, due to its discontinuous sampling, did not fully capture the peak of TRPC currents. However, due to the ability of the IonWorks Quattro to record from 64 cells per well, the variation from well to well was sufficiently reduced allowing for the development of medium-throughput screening assays. © Copyright 2014, Mary Ann Liebert, Inc. 2014