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Conotoxins (CTXs), with their exquisite specificity and potency, have recently created much excitement as drug leads. However, like most peptides, their beneficial activities may potentially be undermined by susceptibility to proteolysis in vivo. By cyclizing the [alpha]-CTX MII by using a range of linkers, we have engineered peptides that preserve their full activity but have greatly improved resistance to proteolytic degradation. The cyclic MII analogue containing a seven-residue linker joining the N and C termini was as active and selective as the native peptide for native and recombinant neuronal nicotinic acetylcholine receptor subtypes present in bovine chromaffin cells and expressed in Xenopus oocytes, respectively. Furthermore, its resistance to proteolysis against a specific protease and in human plasma was significantly improved. More generally, to our knowledge, this report is the first on the cyclization of disulfide-rich toxins. Cyclization strategies represent an approach for stabilizing bioactive peptides while keeping their full potencies and should boost applications of peptide-based drugs in human medicine. conotoxins | drug delivery | molecular engineering

Research has been conducted on the peptide toxin isolated from a spider venom. The primary sequence and three-dimensional structure of this toxin have been investigated via the use of the NMR spectroscopy and the results indicate that in solution the molecule contains conformations produced by the cis/trans isomerization of its proline residue.

The trypsin inhibitor BSTI from Bombina bombina frog consists of 60 residues with five disulfide bonds and a secondary structure of four beta-strands arranged in two antiparallel beta-sheets. BSTI is folded into a disc shape with no hydrophobic core and the active site located in a loop made of 21-34 residues.

The tertiary structure of retrocyclin-2 is determined in a membrane-mimicking environment and a well-defined [beta]-hairpin structure is present in the presence of SDS micelles. The ability to self-associate has contributed to the high-affinity binding of retrocyclins for glycoproteins by increasing the valency and increasing the ability of retrocyclins to cross-link cell surface glycoproteins.

The three-dimensional structure determined using (super 1)H NMR spectroscopy is presented and the potent insecticidal activity for one of these peptides, kalata B2 is demonstrated. Examination of the sequence reveals that they could be separated in to two subfamilies, one of which contains a larger number of positively charged residues and has a bracelet-like circularization of the backbone, and the other contains a backbone twist due to a cis-peptidyl-proline bond and might conceptually be regarded as a molecular Mobius strip.

Research has been conducted on amino acid bacterial peptide microcin J25. The authors have discovered that this peptide does not have a head-to-tail cyclic structure but possesses side chain to backbone cyclization.