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Document Type |
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Article In Journal |
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Document Title |
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SYNTHESIS AND H NMR spectroscopic studies of partially deutera n-propionyl derivative of chiral auxiliary chiracamphox spiro-oxazolidin-2-one تحضير ودراسات H NMR الطيفية مشتقة جزئيا N-بروبيونيل deutera من chiracamphox مساعدة مراوان سبيرو-oxazolidin-2-1 |
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Subject |
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SYNTHESIS AND H NMR spectroscopic studies of partially deutera n-propionyl derivative of chiral auxiliary chiracamphox spiro-oxazolidin-2-one |
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Document Language |
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English |
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Abstract |
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Agitoxin 2 (AgTx2) is a 38-residue scorpion toxin, cross-linked by three disulfide bridges, which acts on
voltage-gated K+ (Kv) channels. Maurotoxin (MTX) is a 34-residue scorpion toxin with an uncommon
four-disulfide bridge reticulation, acting on both Ca2+-activated and Kv channels. A 39-mer chimeric
peptide, named AgTx2-MTX, was designed from the sequence of the two toxins and chemically synthesized.
It encompasses residues 1–5 of AgTx2, followed by the complete sequence of MTX. As established by
enzyme cleavage, the new AgTx2-MTX molecule displays half-cystine pairings of the type C1–C5, C2–C6,
C3–C7, and C4–C8, which is different from that of MTX. The 3D structure of AgTx2-MTX solved by
1H-NMR, revealed both a-helical and b-sheet structures, consistent with a common a/b scaffold of scorpion
toxins. Pharmacological assays of AgTx2-MTX revealed that this new molecule is more potent than both
original toxins in blocking rat Kv1.2 channel. Docking simulations, performed with the 3D structure of
AgTx2-MTX, confirmed this result and demonstrated the participation of the N-terminal domain of AgTx2
in its increased affinity for Kv1.2 through additional molecular contacts. Altogether, the data indicated that
replacement of the N-terminal domain of MTX by the one of AgTx2 in the AgTx2-MTX chimera results |
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ISSN |
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0961-8368 |
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Journal Name |
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Protein Science |
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Volume |
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17 |
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Issue Number |
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1 |
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Publishing Year |
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1428 AH
2008 AD |
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Article Type |
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Article |
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Added Date |
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Sunday, March 24, 2013 |
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Researchers
| صالح طارق جمال | Jamal, Saleh Tariq | Researcher | Doctorate | |
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