Proteases as catalysts for enzymic syntheses of opioid peptides.

Kullmann, Willi

doi:10.1016/s0021-9258(19)70636-x

Cited by 63 publications

(6 citation statements)

References 24 publications

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“…If hydrophobic bonding were the only factor that stabilizes the ligand-RMP complex, however, one should expect that ligand binding would give positive AH°' terms within the experimental temperature range because of the endothermicity of the transfer of nonpolar amino acid side chains from water to the hydrophobic interior of a protein at temperatures below 40 to 50 °C. [49][50][51][52][53][54][55][56][57][58][59][60][61] The present study, however, shows that the binding to RMP of [Leu]-enkephalin is exothermic (AH0/ < 0) for temperatures within the range 5-35 °C. Thus, in addition to the above entropy term, some source of enthalpy stabilization must be involved in the process of drug-RMP association.…”

Section: Discussionmentioning

confidence: 69%

Design, synthesis, and binding characteristics of an opiate receptor mimetic peptide

Kullmann

1984

J. Med. Chem.

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An artificial tetracontapeptide that mimicked the recognition/binding properties of naturally occurring opioid receptors was designed, synthesized, and purified to homogeneity. The design of the primary structure of the receptor mimetic peptide (RMP) accounted for secondary structure prediction rules and for the stereochemical anatomy of various enkephalin and morphine derivatives. The affinity of a series of opioid and nonopioid peptides to RMP was determined from their potency in displacing the binding of enzymatically prepared (14C)-[Leu]-enkephalin. The competition studies revealed that the binding is specific for endogenous opiate peptides, stereoselective for the naturally occurring L isomer of [Leu]-enkephalin, and discriminative for closely related opioid peptides. The thermodynamic parameters associated with the binding of [Leu]-enkephalin to RMP were evaluated from equilibrium studies at different temperatures. The van't Hoff plot of the resulting data was curvilinear. The formation of the ligand--RMP complex was characterized by a decrease both in entropy and in enthalpy with temperature. The thermodynamic behavior provided some evidence that hydrophobic interactions played a prominent role in stabilizing the [Leu]-enkephalin--RMP complex.

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Section: Discussionmentioning

confidence: 69%

Design, synthesis, and binding characteristics of an opiate receptor mimetic peptide

Kullmann

1984

J. Med. Chem.

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“…SPPS requires lengthy protection–deprotection iterations, costly equipment, and the use of toxic reagents . The yields of α-polypeptide from recombinant DNA production are often low and purification can be laborious. , Enzymes, including, amino acid ligases and proteases, have been shown to mediate the formation of peptide bonds between α-amino acid monomers. , Proteases are of particular interest because of their well-studied structure–function relationship. , Protease-mediated α-polypeptide synthesis follows either thermodynamically or kinetically controlled reaction mechanism . Any protease is suitable for the thermodynamically controlled process, where the protease increases the rate at which equilibrium is established but does not influence the equilibrium .…”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Synthesis of Poly(l-alanine) in Aqueous Environment

Baker

Numata

2012

Biomacromolecules

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L-alanine ethyl ester was polymerized into poly(L-alanine) (polyAla), one of the insoluble polypeptides, by papain in aqueous buffer at varying pH. At neutral pH, a maximum chain length of 11 repeats was observed. These polymers were dominated by random coiled structure and demonstrated a lack of patterned macromolecular assembly. Under alkaline conditions, longer polymer chain lengths were achieved, and the maximum chain length was 16 repeats. These longer chains showed distinct β-sheet formation and were capable of fibril assembly. The present study reports on chemoenzymatic synthesis of a hydrophobic homopolypeptide under aqueous conditions as well as demonstrates a chain length dependency of secondary structure formation and macromolecular assembly of chemoenzymatically synthesized polyAla, providing a new insight into material design of polypeptide.

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“…The number of TFA and H20 in the formula of products were determined by CHN analysis. H-Ser-Lys-Cys-Phe-OH-2TFA (1). The protected peptide resin intermediate H-Ser(Bzl)-Lys(Cl-Z)-Cys(MeOBzl)-Phe-Merrifield resin was prepared in four cycles of solid-phase synthesis with an automated Biosearch 9500 Peptide Synthesizer using 2 g of Boc-Phe-Merrifield resin (0.6 mequiv/g).…”

Section: Resultsmentioning

confidence: 99%

“…In this paper we report the selective thiol alkylation of an unprotected model tetrapeptide with various alkylation agents in good yields. The methodology is also applicable to the synthesis of cyclic peptides through intramolecular cysteine alkylation and provides a useful alternative to cyclizations that occur (1) Means, G. E.; Feeney, R. E. Chemical Modifications of Proteins;…”

Section: Introductionmentioning

confidence: 99%