Preparation and Use of a General Solid-Phase Intermediate to Biomimetic Scaffolds and Peptide Condensations

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
J Geno SamaritoniWilliam L Scott

Abstract

The Distributed Drug Discovery (D3) program develops simple, powerful, and reproducible procedures to enable the distributed synthesis of large numbers of potential drugs for neglected diseases. The synthetic protocols are solid-phase based and inspired by published work. One promising article reported that many biomimetic molecules based on diverse scaffolds with three or more sites of variable substitution can be synthesized in one or two steps from a common key aldehyde intermediate. This intermediate was prepared by the ozonolysis of a precursor functionalized at two variable sites, restricting their presence in the subsequently formed scaffolds to ozone compatible functional groups. To broaden the scope of the groups available at one of these variable sites, we developed a synthetic route to an alternative, orthogonally protected key intermediate that allows the incorporation of ozone sensitive groups after the ozonolysis step. The utility of this orthogonally protected intermediate is demonstrated in the synthesis of several representative biomimetic scaffolds containing ozonolytically labile functional groups. It is compatible with traditional Fmoc peptide chemistry, permitting it to incorporate peptide fragments for use...Continue Reading

References

Sep 15, 1977·Journal of Molecular Biology·P Y Chou, G D Fasman
Aug 1, 1991·International Journal of Peptide and Protein Research·W J van Woerkom, J W van Nispen
Apr 20, 1973·Biochimica Et Biophysica Acta·P N LewisH A Scheraga
Aug 14, 1968·Journal of the American Chemical Society·M A OndettiM Bodanszky
Dec 31, 1982·Biochemical and Biophysical Research Communications·J L KrstenanskyB L Currie
Oct 29, 1993·Journal of Medicinal Chemistry·M J GeninR L Johnson
Aug 6, 1993·Journal of Medicinal Chemistry·N L SubasingheR L Johnson
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·Clay Fuqua, E Peter Greenberg
Sep 15, 2005·Journal of the American Chemical Society·Grant D GeskeHelen E Blackwell
May 17, 2007·Journal of the American Chemical Society·William L ScottMartin J O'Donnell
Jan 27, 2009·Chemical Society Reviews·Stephen B H Kent
Jan 27, 2009·Chemical Society Reviews·Eric Valeur, Mark Bradley
May 30, 2013·Organic & Biomolecular Chemistry·Paul M LevineKent Kirshenbaum
Jan 18, 2014·Chembiochem : a European Journal of Chemical Biology·Mette R HansenThomas E Nielsen
Feb 27, 2015·Bioorganic & Medicinal Chemistry·Mette R HansenThomas E Nielsen

❮ Previous
Next ❯

Methods Mentioned

BETA
acylation
reverse-phase chromatography
NMR
x-ray crystallography
circular dichroism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.