Structural requirements for inhibition of polyphenylalanine synthesis by aminoacyl and nucleotidyl analogues of puromycin

Symons, Robert H.; Harris, Rose; Clarke, Lyndall P.; Wheldrake, J.F.; Elliott, William H.

doi:10.1016/0005-2787(69)90146-4

Cited by 47 publications

(16 citation statements)

References 3 publications

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“…Removal of the p-OMe group from the aromatic moieties did not alter the activity of the puromycin analogues (Table 1), whereas a 2.3-fold decrease in activity was noted in the chloramphenicol derivatives ( Table 2). The decreased activity noted for the L-Leu puromycin analogue (Table 1) is consistent with previous observations that replacement of the aromatic amino acid with a nonaromatic moiety greatly decreases activity (9,16,18). In contrast, however, the L-Phe and L-Leu chloramphenicol analogues (Table 2) exhibited little or no difference in effects on protein synthesis.…”

Section: Resultssupporting

confidence: 89%

Chloramphenicol Binding Site with Analogues of Chloramphenicol and Puromycin

Vince

Almquist

Ritter

et al. 1975

Antimicrob Agents Chemother

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The effect of a series of puromycin analogues and aminoacyl chloramphenicol derivatives on poly(U,C)-directed polyphenylalanine synthesis in an Escherichia coli cell-free system was examined. A comparison between the structures and activities of the puromycin and chloramphenicol analogues was made to examine the proposal that ribosomal binding sites for both antibiotics overlap. Our results suggest that the dichloroacetamido group in the chloramphenicol molecule does not correspond to the role of the aminoacyl moieties of either puromycin or aminoacyl transfer ribonucleic acid. These results comparing the structures and activities of puromycin and chloramphenicol analogues also seem inconsistent with a common binding site for the p -substituted phenyl moieties of the two antibiotics. Previous data have indicated that both sites are mutually affected by the prior binding of either antibiotic. Although it is possible that chloramphenicol and puromycin may have overlapping bindings sites, no common structural features between the two antibiotics are supported by our data.

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Section: Resultssupporting

confidence: 89%

Chloramphenicol Binding Site with Analogues of Chloramphenicol and Puromycin

Vince

Almquist

Ritter

et al. 1975

Antimicrob Agents Chemother

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“…I n their pioneering work, Nathans and Neidle [6] and later Symons, Harris, Clarke, Wheldrake and Elliot [28] observed that protein synthesis is inhibited only by those derivatives of puromycin which contain a p-methoxyphenylalanine or a phenylalanine residue while derivatives with a different amino acid were practically inactive. A similar conclusion was reached by Waller et al [9].…”

Section: Products Of the L'ransfer Reactimmentioning

confidence: 99%

Substrate Specificity of Ribosomal Peptidyl Transferase

Rychlík

Černá

Chládek

et al. 1970

European Journal of Biochemistry

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The effect of the nature of the amino acid residue on the acceptor activity of substrates of ribosomal peptidyl transferase was investigated. We tested 2′(3′)‐O‐aminoacyladenosines containing the following amino acid residues: l‐alanine, l‐glutamine, glycine, l‐3‐(1‐benzyl‐4‐imidazolyl)‐alanine, l‐leucine, l‐lysine, l‐methionine, l‐methionine S‐oxide, l‐phenylalanine, d‐phenylalanine, l‐proline, l‐serine and l‐valine as acceptors of the acylaminoacyl residue transferred from peptidyl‐tRNA. The acceptor activity of these compounds was dependent on the nature of the side chain of the amino acid residues bound to adenosine. The acceptor activity was also affected by the nature of the donor tRNA derivative. With l‐acetylphenylalanyl‐tRNA or l‐acetylleucine npetanucleotide fragments derived from l‐acetylleucyl‐tRNA donating the acetylphenylalanyl and the acetylleucyl residue, respectively, a high acceptor activity was shown by the basic 2′(3′)‐O‐l‐lysyladenosine or 2′(3′)‐O‐l‐3‐(1‐benzyl‐4‐imidazolyl)‐alanyladenosine which acted only as weak acceptors of lysine peptides from (Lys)n‐tRNA. The transfer reaction catalyzed by peptidyl transferase was stereospecific with respect to acceptor substrates. The acylaminoacyl residue was transferred from tRNA to 2′(3′)‐O‐l‐phenylalanyladenosine, whereas 2′(3′)‐O‐d‐phenylalanyladenosine, containing a d‐phenylalanine residue, was completely inactive as acceptor.

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“…The puromycin analogs of those amino acids inhibited the protein synthesis and formed peptidyl puromycin in the ribosome [7,8]. On the other hand, those of low activity may either have low affinity for the active center, or effectively bind to the active center but do not react with peptidyl tRNA.…”

Section: Discussionmentioning

confidence: 99%

“…For example, L-2-phenanthrylalanine that occupies regions B, E and H may adapt, whereas L-1-phenanthrylalanine that occupies regions A, B and D will not. This model explains that the analogs with benzyl derivatives of L-serine and L-cysteine are active [7,8], because the benzene rings of these derivatives are located in region E.…”

Section: Febs Letters November 1993mentioning

confidence: 99%

“…The inhibitory activity of puromytin analogs has been examined as a measure for the adaptability of amino acids to the active center of ribosomal A site. The analogs of aromatic amino acids, L-phenylalanine and L-tyrosine were most effective [6-81, and those with 0-benzyl+serine, S-benzyl-Lcysteine [7,8], L-homocitrulline [9] and L-lysine [lo] were moderately active, whereas the analogs of other amino acids were almost inactive. The optical configuration of the amino acids was also important since the D-phenylalanyl analog was far less active than the L-isomer [6].…”

Section: Introductionmentioning

confidence: 99%

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Adaptability of nonnatural aromatic amino acids to the active center of the E. coli ribosomal A site

et al. 1993

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-Aminoacyl analogs of puromycin with nonnatural aromatic amino acids were synthesized and their inhibitory activity in E. coli in vitro protein synthesizing system was evaluated. The analogs with L-2-naphthylalanine, L-p-biphenylalanine, L-2-anthrylalanine and trans+p-phenylazophenylalanine were found to inhibit the protein synthesis with high efficiency. The inhibition suggests that these nonnatural amino acids are accepted by the active center of the E. coli ribosomal A site. A model for the adaptability of nonnatural aromatic amino acids to the active center is proposed.

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Structural requirements for inhibition of polyphenylalanine synthesis by aminoacyl and nucleotidyl analogues of puromycin

Cited by 47 publications

References 3 publications

Chloramphenicol Binding Site with Analogues of Chloramphenicol and Puromycin

Chloramphenicol Binding Site with Analogues of Chloramphenicol and Puromycin

Substrate Specificity of Ribosomal Peptidyl Transferase

Adaptability of nonnatural aromatic amino acids to the active center of the E. coli ribosomal A site

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