PART 2: CONVERSION OF THE ACTIVE DOMAIN OF NATURAL OPOSSUM LETHAL, TOXIN NEUTRALIZING......


By jpeza - Posted on 26 Junio 2009

Fecha Publicación: 
1 Ene 2008
Nombre de Revista: 
Datos del paper
Autor Principal: 
BINIE VER LIPPS
Volumen: 
27
Issue: 
2
Página Inicial: 
93
Página Final: 
107
Abstract: 

Lethal toxin neutrakizing factor (LTW), ruhich was isolated from opossurn

serwrn, has a molecular weight of 63 kDa and is a potent antidote for toxins

fwrn animal, plant, and bactmia. This rtmieui describes studies leading to the

idcnt~jication of a srnall fragrnent of L T m which ekicited anti-lethal activity

against a~uimal,p lant, and bacterial toxins s~rr~ilator intact natural L T M

Ident~jication of an active fragmcnt srnall enough to make a synthehc vmion

of this amazing ,molecule was vimed as a key step in the process of dtmeloping

an effective agent for anti-venwrn and anti-toxin therapy. Purijied L T W was

treated with trypsin to cause fragmentation at the argiruine and lysine sites. The

fragrnents rum separated by high-presswre liquid chrwrnatography (HPLC) and

were tested for abikty to bind to anti-LTNFand inhibit anti-LTW binding in an

cnzyme-linked zrnmunos~rbent assay (ELISA). The fragment showing the ,most

binding to anti-LTW was sequenced. Synthetic peptides consisting of 15 and

10 amino acids frwrn the N-tminal was constructed and designated as LT-15,

having artrino acid sequence, Leu-Lys-Ala-Met-As@-Tt~r-Pr~Pro-Le?!-Trp-Ile-

Lys-Thr-Glu and LT-10 having sequence Leu-Lys-Ala-Met-AspPr~Tlir-PrpPr~

Leu. Death of mice due to intra-~rnusculari njection of Predeterrtrined lethal doses

of toxins derived from awimal, plant, and bacterial sources íuas prwented by

treatrnent with synthetic peptides LT-15 and LTIO. The lethality ruas inhibited

when the treatment wus given before or afta. toxin iyection. LT-10 can be mude

ir1 abundante by cherr~icasl ynthesis arul has the poter~tialt o becwrne a universal

tho.ni;y agcinst intoxication caused by animal, plar~t, and bacterial toxins.

Dirección del Autor: 

Ophidia Products, Iric., Bellaire, Texas, USA

Keywords: 
lethal toxin neutralizirig factor
active fragment
synthetic
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