Structure-activity relationship of chlorotoxin-like peptides

Ali, Syed Abid, Alam, Mehtab, Abbasi, Atiya, Undheim, Eivind A. B., Fry, Bryan Grieg, Kalbacher, Hubert and Voelter, Wolfgang (2016) Structure-activity relationship of chlorotoxin-like peptides. Toxins, 8 2: . doi:10.3390/toxins8020036


Author Ali, Syed Abid
Alam, Mehtab
Abbasi, Atiya
Undheim, Eivind A. B.
Fry, Bryan Grieg
Kalbacher, Hubert
Voelter, Wolfgang
Title Structure-activity relationship of chlorotoxin-like peptides
Journal name Toxins   Check publisher's open access policy
ISSN 2072-6651
Publication date 2016-02-02
Sub-type Article (original research)
DOI 10.3390/toxins8020036
Open Access Status DOI
Volume 8
Issue 2
Total pages 18
Place of publication Basel, Switzerland
Publisher MDPI
Collection year 2017
Language eng
Formatted abstract
Animal venom (e.g., scorpion) is a rich source of various protein and peptide toxins with diverse physio-/pharmaco-logical activities, which generally exert their action via target-specific modulation of different ion channel functions. Scorpion venoms are among the most widely-known source of peptidyl neurotoxins used for callipering different ion channels, such as; Na+, K+, Ca+, Cl, etc. A new peptide of the chlorotoxin family (i.e., Bs-Tx7) has been isolated, sequenced and synthesized from scorpion Buthus sindicus (family Buthidae) venom. This peptide demonstrates 66% with chlorotoxin (ClTx) and 82% with CFTR channel inhibitor (GaTx1) sequence identities reported from Leiurus quinquestriatus hebraeus venom. The toxin has a molecular mass of 3821 Da and possesses four intra-chain disulphide bonds. Amino acid sequence analysis of Bs-Tx7 revealed the presence of a scissile peptide bond (i.e., Gly-Ile) for human MMP2, whose activity is increased in the case of tumour malignancy. The effect of hMMP2 on Bs-Tx7, or vice versa, observed using the FRET peptide substrate with methoxycoumarin (Mca)/dinitrophenyl (Dnp) as fluorophore/quencher, designed and synthesized to obtain the lowest Km value for this substrate, showed approximately a 60% increase in the activity of hMMP2 upon incubation of Bs-Tx7 with the enzyme at a micromolar concentration (4 µM), indicating the importance of this toxin in diseases associated with decreased MMP2 activity.
Keyword CFTR
Chloride channel
Chlorotoxin
MMP2
Peptidyl-inhibitors
Scorpion venom
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Article number 36

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biological Sciences Publications
 
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