Ribosome-catalyzed formation of an abnormal peptide analog

Roesser, James R.; Chorghade, Mukund S.; Hecht, Sidney M.

doi:10.1021/bi00369a003

Cited by 55 publications

(31 citation statements)

References 32 publications

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“…This figure was constructed in collaboration with Dr. James C. Powers et al 2008; Tan et al 2004;Victorova et al 1976). Sidney Hecht reported ribosomal reaction products with altered connectivity, resulting from nucleophilic attack at other than the usual C 0 atom (Roesser et al 1986). He originated the hypothesis that the PTC speeds up reactions but does not perform standard catalytic functions (i.e., it does not specifically stabilize the transition state).…”

Section: Making Peptide Bondsmentioning

confidence: 99%

The Ribosome Challenge to the RNA World

2015

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An RNA World that predated the modern world of polypeptide and polynucleotide is one of the most widely accepted models in origin of life research. In this model, the translation system shepherded the RNA World into the extant biology of DNA, RNA, and protein. Here, we examine the RNA World Hypothesis in the context of increasingly detailed information available about the origins, evolution, functions, and mechanisms of the translation system. We conclude that the translation system presents critical challenges to RNA World Hypotheses. Firstly, a timeline of the RNA World is problematic when the ribosome is incorporated. The mechanism of peptidyl transfer of the ribosome appears distinct from evolved enzymes, signaling origins in a chemical rather than biological milieu. Secondly, we have no evidence that the basic biochemical toolset of life is subject to substantive change by Darwinian evolution, as required for the transition from the RNA world to extant biology. Thirdly, we do not see specific evidence for biological takeover of ribozyme function by protein enzymes. Finally, we can find no basis for preservation of the ribosome as ribozyme or the universality of translation, if it were the case that other information transducing ribozymes, such as ribozyme polymerases, were replaced by protein analogs and erased from the phylogenetic record. We suggest that an updated model of the RNA World should address the current state of knowledge of the translation system.

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Section: Making Peptide Bondsmentioning

confidence: 99%

The Ribosome Challenge to the RNA World

2015

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“…[116] A number of unnatural amino acids were incorporated into the first position of dipeptides by this method. [117][118][119] However, this approach suffered a number of limitations: yields of the aminoacylation reaction were quite poor and the N-terminal protecting group of the amino acid could not be efficiently removed without hydrolysis of the aminoacyl ester, thereby limiting substitution to P-site donors and, consequently, the peptide N-terminus ( Figure 5). Later, Brunner and co-workers developed a method to prepare a fully deprotected aminoacyl-pCpA and ligate it to the truncated tRNA to afford an aminoacyl tRNA which could be used as an A-site donor.…”

Section: Protein Sciencementioning

confidence: 99%

Expanding the Genetic Code

2004

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Although chemists can synthesize virtually any small organic molecule, our ability to rationally manipulate the structures of proteins is quite limited, despite their involvement in virtually every life process. For most proteins, modifications are largely restricted to substitutions among the common 20 amino acids. Herein we describe recent advances that make it possible to add new building blocks to the genetic codes of both prokaryotic and eukaryotic organisms. Over 30 novel amino acids have been genetically encoded in response to unique triplet and quadruplet codons including fluorescent, photoreactive, and redox-active amino acids, glycosylated amino acids, and amino acids with keto, azido, acetylenic, and heavy-atom-containing side chains. By removing the limitations imposed by the existing 20 amino acid code, it should be possible to generate proteins and perhaps entire organisms with new or enhanced properties.

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“…Bei diesen Versuchen, die sich auf vorhergehende Arbeiten mit Amber-Suppressoren stützten, [8,54] wurden in erster Linie aminoacylierte tRNAs mit erweiterten Anticodons in In-vitro-Translationssystemen eingesetzt. [55][56][57] Weiterführende Ansätze beruhten auf der Mikroinjektion von aminoacylierten tRNAs mit erweiterten Anticodons in Xenopus-Oozyten. [58][59][60] Bei dieser Vorgehensweise wird die tRNA vor der Zugabe zum Translationsgemisch aminoacyliert.…”

Section: Codierung Nichtnatürlicher Aminosäuren An Quadruplettcodonsunclassified

Die Umprogrammierung des genetischen Codes: vom Triplett‐ zum Quadruplettcode

2012

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Der genetische Code lebender Zellen ist nahezu universell ein Triplettcode. Zelluläre Ribosomen so zu verändern, dass sie auch andere als Triplettcodes ablesen können, stellt eine große Herausforderung dar, da viele ribosomale Mutationen letal sind. In diesem Kurzaufsatz diskutieren wir den Einbau nichtnatürlicher Aminosäuren in Proteine durch Ablesen von Quadruplettcodons sowie die Entwicklung eines orthogonalen Translationssystems in der Zelle, das sich eines evolvierten orthogonalen Ribosoms bedient, um durch Ablesen von Quadruplettcodons in effizienter Weise den Einbau nichtnatürlicher Aminosäuren in Proteine zu dirigieren. Durch Verwendung dieses Systems gelang der Einbau von multiplen nichtnatürlichen Aminosäuren, um rekombinante Proteine auf genetischem Wege mit emergenten Eigenschaften auszustatten. Die Ausweitung dieses Ansatzes könnte die kombinatorische Biosynthese von Materialien und Therapeutika möglich machen und darüber hinaus die Erforschung der Frage anspornen, ob sich Lebensformen mit zusätzlichen genetisch codierten Polymeren entwickeln könnten, die Aufgaben erfüllen, die natürliche biologische Systeme nicht ausführen.

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Ribosome-catalyzed formation of an abnormal peptide analog

Cited by 55 publications

References 32 publications

The Ribosome Challenge to the RNA World

The Ribosome Challenge to the RNA World

Expanding the Genetic Code

Die Umprogrammierung des genetischen Codes: vom Triplett‐ zum Quadruplettcode

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