title: Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities.
abstract: Here we report two novel 17-mer amidated linear peptides (TsAP-1 and TsAP-2) whose structures were deduced from cDNAs cloned from a venom-derived cDNA library of the Brazilian yellow scorpion, Tityus serrulatus. Both mature peptides were structurally-characterised following their location in chromatographic fractions of venom and synthetic replicates of each were subjected to a range of biological assays. The peptides were each active against model test micro-organisms but with different potencies. TsAP-1 was of low potency against all three test organisms (MICs 120-160 μM), whereas TsAP-2 was of high potency against the Gram-positive bacterium, Staphylococcus aureus (MIC 5 μM) and the yeast, Candida albicans (10 μM). Haemolytic activity of TsAP-1 was low (4% at 160 μM) and in contrast, that of TsAP-2 was considerably higher (18% at 20 μM). Substitution of four neutral amino acid residues with Lys residues in each peptide had dramatic effects on their antimicrobial potencies and haemolytic activities, particularly those of TsAP-1. The MICs of the enhanced cationic analogue (TsAP-S1) were 2.5 μM for S. aureus/C. albicans and 5 μM for E. coli but with an associated large increase in haemolytic activity (30% at 5 μM). The same Lys residue substitutions in TsAP-2 produced a dramatic effect on its MIC for E. coli lowering this from >320 μM to 5 μM. TsAP-1 was ineffective against three of the five human cancer cell lines tested while TsAP-2 inhibited the growth of all five. Lys residue substitution of both peptides enhanced their potency against all five cell lines with TsAp-S2 being the most potent with IC50 values ranging between 0.83 and 2.0 μM. TsAP-1 and TsAP-2 are novel scorpion venom peptides with broad spectrum antimicrobial and anticancer cell activities the potencies of which can be significantly enhanced by increasing their cationicity.
authors.affiliation: Molecular Therapeutics Research, School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Guo
authors.forename: Chengbang
authors.initials: C
authors.lastname: Ma
authors.forename: Qiang
authors.initials: Q
authors.lastname: Du
authors.forename: Ran
authors.initials: R
authors.lastname: Wei
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001483:Base Sequence; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000737:chemistry*; D012605:Scorpions; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D018076:DNA, Complementary; D004220:Disulfides; D010455:Peptides; D012604:Scorpion Venoms
keywords: Antimicrobial; Molecular cloning; Peptide; Scorpion