Myotoxic phospholipases A(2) isolated from Bothrops brazili snake venom and synthetic peptides derived from their C-terminal region: Cytotoxic effect on microorganism and tumor cells

This paper reports the purification and biochemical/pharmacological characterization of two myotoxic phospholipases A(2) (PLA(2)S) from Bothrops brazili venom, a native snake from Brazil. Both myotoxins (MTX-I and II) were purified by a single chromatographic step on a CM-Sepharose ion-exchange column up to a high purity level, showing M-r similar to 14,000 for the monomer and 28,000 Da for the dimer. The N-terminal and internal peptide amino acid sequences showed similarity with other myotoxic PLA2S from snake venoms, MTX-I belonging to Asp49 PLA(2) class, enzymatically active, and MTX-II to Lys49 PLA(2)S, catalytically inactive. Treatment of MTX-I with BPB and EDTA reduced drastically its PLA(2) and anticoagulant activities, corroborating the importance of residue His48 and Ca2+ ions for the enzymatic catalysis. Both PLA(2)S induced myotoxic activity and dose-time dependent edema similar to other isolated snake venom toxins from Bothrops and Crotalus genus. The results also demonstrated that MTXs and cationic synthetic peptides derived from their 115-129 C-terminal region displayed cytotoxic activity on human T-cell leukemia (JURKAT) lines and microbicidal effects against Escherichia coli, Candida albicans and Leishmania sp. Thus, these PLA(2) proteins and C-terminal synthetic peptides present multifunctional properties that might be of interest in the development of therapeutic strategies against parasites, bacteria and cancer. (C) 2008 Elsevier Inc. All rights reserved.

Antitumor effects of snake venom chemically modified Lys49 phospholipase A(2)-like BthTX-I and a synthetic peptide derived from its C-terminal region

The present work evaluates both in vitro and in vivo antitumor activity of BPB-modified BthTX-I and its cationic synthetic peptide derived from the 115-129 C-terminal region. BPB-BthTX-1 presented cytotoxicity of 10-40% on different tumor cell lines, which were also susceptible to the lytic action of the synthetic peptide. Injection of the modified protein or the peptide in mice, 5 days after transplantation of S 180 tumor cells, reduced 30 and 36% of the tumor size on day 14th and 76 and 79% on day 60th, respectively, when compared to the untreated control group. Thus, these antitumor properties might be of interest in the development of therapeutic strategies against cancer. (C) 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Outdoor room, T House, Sunshine Coast

As seen from mezzanine.

View to house through scrub, T House, Sunshine Coast

Deck on left, with opening to outdoor room on right.

Daybed alcove, T House, Sunshine Coast

Exterior of alcove to outdoor room.

Entry, T House, Sunshine Coast

Entry from deck and seating area to outdoor room.

Window, Lake Weyba House, Sunshine Coast

Vinyl window to daybed alcove, bedroom pavilion, South-West elevation.

Window, Lake Weyba House, Sunshine Coast

Vinyl window to bath house pavilion, South-West elevation.

Main Pavilion, Lake Weyba House, Sunshine Coast

As seen from West, looking towards front of main pavilion. Standard roller doors to clerestory.

Pivoting vent, Lake Weyba House, Sunshine Coast

Bedroom pavilion, South-East elevation. Day bed alcove on left.

Pavilions and outdoor seating area, Lake Weyba House, Sunshine Coast

As seen from back of bedroom pavilion, looking towards main pavilion. Day bed alcove to bedroom in foreground.

South-West elevation, Lake Weyba House, Sunshine Coast

Bath house and bedroom pavilions, with outdoor seating area in foreground.

Main pavilion, Lake Weyba House, Sunshine Coast

South-West elevation of main pavilion - living, kitchen, dining and study/guest areas.