Discovery, synthesis, and structure–activity relationships of conotoxins

KB Akondi, M Muttenthaler, S Dutertre, Q Kaas… - Chemical …, 2014 - ACS Publications
Peptide therapeutics are acclaimed as a promising addition to the pharmaceutical arena,
and they continue to attract interest due to their high potency, bioavailability, and fewer …

The cystine knot motif in toxins and implications for drug design

DJ Craik, NL Daly, C Waine - Toxicon, 2001 - Elsevier
The cystine knot structural motif is present in peptides and proteins from a variety of species,
including fungi, plants, marine molluscs, insects and spiders. It comprises an embedded ring …

Folding of Conotoxins: Formation of the Native Disulfide Bridges During Chemical Synthesis and Biosynthesis of Conus Peptides

G Bulaj, BM Olivera - Antioxidants & redox signaling, 2008 - liebertpub.com
Conopeptides from> 700 species of predatory marine Conus snails provide an impressive
molecular diversity of cysteine-rich peptides. Most of the estimated 50,000–100,000 distinct …

Voltage-gated calcium channels as targets for the treatment of chronic pain

JG McGivern, SI McDonough - Current Drug Targets-CNS & …, 2004 - ingentaconnect.com
This review focuses on the importance of voltage-gated calcium channels in modulating and
controlling the function of peripheral and central neurons involved in nociceptive processing …

Less is more: design of a highly stable disulfide-deleted mutant of analgesic cyclic α-conotoxin Vc1. 1

R Yu, VAL Seymour, G Berecki, X Jia, M Akcan… - Scientific reports, 2015 - nature.com
Abstract Cyclic α-conotoxin Vc1. 1 (cVc1. 1) is an orally active peptide with analgesic activity
in rat models of neuropathic pain. It has two disulfide bonds, which can have three different …

Structures of μO-conotoxins from Conus marmoreus: Inhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons

NL Daly, JA Ekberg, L Thomas, DJ Adams… - Journal of Biological …, 2004 - ASBMB
The μO-conotoxins are an intriguing class of conotoxins targeting various voltage-
dependent sodium channels and molluscan calcium channels. In the current study, we have …

Structure of the analgesic μ-conotoxin KIIIA and effects on the structure and function of disulfide deletion

KK Khoo, ZP Feng, BJ Smith, MM Zhang… - Biochemistry, 2009 - ACS Publications
μ-Conotoxin μ-KIIIA, from Conus kinoshitai, blocks mammalian neuronal voltage-gated
sodium channels (VGSCs) and is a potent analgesic following systemic administration in …

Cyclic analogues of α‐conotoxin Vc1. 1 inhibit colonic nociceptors and provide analgesia in a mouse model of chronic abdominal pain

J Castro, L Grundy, A Deiteren… - British journal of …, 2018 - Wiley Online Library
Background and Purpose Patients with irritable bowel syndrome suffer from chronic visceral
pain (CVP) and limited analgesic therapeutic options are currently available. We have …

Early engineering approaches to improve peptide developability and manufacturability

JL Furman, M Chiu, MJ Hunter - The AAPS journal, 2015 - Springer
Abstract Downstream success in Pharmaceutical Development requires thoughtful molecule
design early in the lifetime of any potential therapeutic. Most therapeutic monoclonal …

Role of Hydroxyprolines in the in Vitro Oxidative Folding and Biological Activity of Conotoxins

E Lopez-Vera, A Walewska, JJ Skalicky, BM Olivera… - Biochemistry, 2008 - ACS Publications
Hydroxylation of proline residue occurs in specific peptides and proteins derived from plants
and animals, but the functional role of this modification has been characterized primarily in …