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Viktor Krchnak

Publications and source records attributed to Viktor Krchnak.

4 recordsLinked to original sources
PubMed2006

Synthesis of an inhibitor-tethered resin for detection of active matrix metalloproteinases involved in disease.

Matrix metalloproteinases (MMPs), of which 26 members are known in humans, are implicated in a number of diseases. Their activity is strictly controlled, but when the biological control over the activity is lost, disease processes set in. In an attempt to delineate what MMP activity has gone awry in what diseases, including metastatic cancers that are of special interest to our laboratories, we conceived and synthesized two chromatographic resins incorporated with a multifunctional broad-spectrum inhibitor for MMPs. The broad-spectrum inhibitor contains three sterogentic centers and was synthesized in 13 steps. Two structural variants of the inhibitors were linked to the polymer support via disulfide moieties. These resins are intended for use in cellular systems to selectively fish out from a complex mixture of all cellular proteins the active MMP forms important for the specific disease for identification.

Disease↗
PubMedDate not supplied

Simple tools for resin distribution.

Two simple instruments allowing uniform distribution of resin beads for solid-phase synthesis are described. The first tool simplifies distribution of resin into microtiterplates. The second tool was designed for distribution of a variable amount of resin beads into any number of reaction vessels, and the technique is applicable to resin beads with a wide range of physical properties (density).

Amino Acids↗
PubMedDate not supplied

Polymer-supported N-derivatized, o-linked hydroxylamine for concurrent solid-phase synthesis of diverse N-alkyl and N-H hydroxamates.

We describe parallel/combinatorial, solid-phase, supported synthesis of diverse hydroxamates using a common intermediate, an N-derivatized, O-linked hydroxylamine. The method allows the concurrent synthesis of both N-alkyl and N-H hydroxamates and is compatible with a wide range of chemical transformations. The synthesis of NH hydroxamates includes protection of the nitrogen with a 2,4-dimethoxybenzyl group at the stage of polymer-supported benzyloxyamine. The protecting group eliminates side reactions caused by the presence of a free hydroxamate NH group and is simultaneously removed during cleavage of target compounds from the solid support. The chemical route has been thoroughly tested on model compounds with several linkers, and a high yield and purity synthesis of more than 50 hydroxamates, designed to inhibit cell proliferation of breast cancer cell lines, is described.

Antineoplastic Agents↗