Chimeric Protein Engineering

Feng, Jianwen; Tessler, Lee A.; Marshall, Garland R.

doi:10.1007/s10989-006-9058-8

Cited by 10 publications

(14 citation statements)

References 28 publications

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“…In further preliminary simulation studies 128 of intact RNase analogs, R-Nip-S-Nip of Arnold et al 116 and other potential replacements of Asn113-Pro114 were compared with native RNase. To investigate the minimal effect on the melting temperature [DT m ¼ (1.2 6 0.3)8C] observed, the crystal structure of RNase was minimized, the turn mimetic R-Nip-S-Nip inserted for Asn113-Pro114 and the chimeric structure reminimized.…”

Section: Simulations Of Chimeric Rnasementioning

confidence: 99%

“…FSD-1 was used as a model system for MD simulations of folding and stability for chimeric proteins incorporating helical mimetics. 128 FSD-1 was chosen as a prototype for chimeric protein engineering because of its small size and because its a-helical segment could be replaced with a semirigid, organic helix mimetic. It should be possible to predict enhanced stability by computational methods due to its small size (28 residues versus 124 residues for RNase).…”

Section: Toward Protein Engineeringmentioning

confidence: 99%

“…Its short b-hairpin peptide segment could be readily synthesized by solid-phase synthesis and chemically ligated to the organic helical mimetic. 128 Experimental observations and theoretical calculations suggested that helical mimetics based on a triphenyl, tripyridyl, or phenyldipyridyl scaffolds could correctly orient the i, i + 3, i + 4, and i + 7 side chains that formed one side of the surface of an a-helix. 89,92,103 To further investigate the stabilities of helix mimetics, chimeric proteins were designed in silico by ligating four different helix mimetic designs with the bhairpin subdomain of FSD-1 ( Figure 16).…”

Section: Toward Protein Engineeringmentioning

confidence: 99%

“…A 100-ns MD simulation with GB/SA implicit solvation showed that one of these chimeric proteins was more stable than the native structure and maintained the expected fold during simulations. 128 More detailed simulations using replica exchange at several temperatures are underway to determine if the melting temperatures of the chimeric proteins can be predicted. Future Studies of Chimeric RNase Proteins.…”

Section: Toward Protein Engineeringmentioning

confidence: 99%

“…128 Impact on stability may have been impacted negatively by difference in torsional barriers as shown in Figure 11. 60 …”

Section: Figure 16mentioning

confidence: 99%

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Back to the future: Ribonuclease A

2008

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Pancreatic ribonuclease A (EC 3.1.27.5, RNase) is, perhaps, the best‐studied enzyme of the 20th century. It was isolated by René Dubos, crystallized by Moses Kunitz, sequenced by Stanford Moore and William Stein, and synthesized in the laboratory of Bruce Merrifield, all at the Rockefeller Institute/University. It has proven to be an excellent model system for many different types of experiments, both as an enzyme and as a well‐characterized protein for biophysical studies. Of major significance was the demonstration by Chris Anfinsen at NIH that the primary sequence of RNase encoded the three‐dimensional structure of the enzyme. Many other prominent protein chemists/enzymologists have utilized RNase as a dominant theme in their research. In this review, the history of RNase and its offspring, RNase S (S‐protein/S‐peptide), will be considered, especially the work in the Merrifield group, as a preface to preliminary data and proposed experiments addressing topics of current interest. These include entropy–enthalpy compensation, entropy of ligand binding, the impact of protein modification on thermal stability, and the role of protein dynamics in enzyme action. In continuing to use RNase as a prototypical enzyme, we stand on the shoulders of the giants of protein chemistry to survey the future. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 259–277, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Section: Simulations Of Chimeric Rnasementioning

confidence: 99%

Section: Toward Protein Engineeringmentioning

confidence: 99%

Section: Toward Protein Engineeringmentioning

confidence: 99%

Section: Toward Protein Engineeringmentioning

confidence: 99%

“…128 Impact on stability may have been impacted negatively by difference in torsional barriers as shown in Figure 11. 60 …”

Section: Figure 16mentioning

confidence: 99%

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Back to the future: Ribonuclease A

2008

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Modification of Peptides to Limit Metabolism

Kumarasinghe

Hruby

2015

Peptide Chemistry and Drug Design

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Synthesis of a cyclic isostere of α-methyl homoserine by a stereoselective acylation–alkylation sequence of a chiral γ-lactam

et al. 2014

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Starting from a chiral 4-hydroxymethyl pyrrolidin-2-one, an isostere of α-methyl homoserine tethered on a γ-lactam ring was prepared exploiting a stereoselective acylation-methylation sequence, followed by Curtius rearrangement, and structural assignment was confirmed by n.O.e. experiments. By reverting the sequence, the 3-carboxy-3-methyl derivative having the opposite configuration at C-3 was obtained with total stereoselection, but Curtius rearrangement invariably afforded only inseparable mixtures of decomposition products.

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Chimeric Protein Engineering

Cited by 10 publications

References 28 publications

Back to the future: Ribonuclease A

Back to the future: Ribonuclease A

Modification of Peptides to Limit Metabolism

Synthesis of a cyclic isostere of α-methyl homoserine by a stereoselective acylation–alkylation sequence of a chiral γ-lactam

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