A Constrained Diketopiperazine as a New Scaffold for the Synthesis of Peptidomimetics

Pons, Jean‐François; Fauchère, Jean‐Luc; Lamaty, Frédéric; Molla, Annie; Lázaro, R.

doi:10.1002/(sici)1099-0690(199805)1998:5<853::aid-ejoc853>3.0.co;2-f

Cited by 35 publications

(25 citation statements)

References 21 publications

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“…Guanidinium hydrochloride, agmatine sulfate, and arginine were obtained commercially (Aldrich). All other guanidinium derivatives shown in Table 1 were prepared by guanylation of the corresponding amines [28] and obtained as hydrochloride salts. Their structures were confirmed by 1 H and 13 C NMR and HRMS (high resolution mass spectrometry).…”

Section: Methodssupporting

confidence: 78%

Characterization of specific noncovalent complexes between guanidinium derivatives and single-stranded DNA by MALDI

Ohara

Smietana

Vasseur

2006

J. Am. Soc. Mass Spectrom.

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Noncovalently bound complexes between highly basic sites of 12 guanidinium compounds and single-stranded DNA were studied using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. 6-Aza-2-thiothymine (ATT) was used as the matrix in the presence of ammonium citrate, and spectra were recorded in the positive ion mode. Detailed control experiments confirmed unambiguously the high selectivity and specificity of the guanidinium moiety for phosphate groups of DNA. The results verify the binding stoichiometry and show preferential binding of hydrophobic binders (pyrene and anthracene guanidinium derivatives) to all sequences examined. In addition, we demonstrate that electrostatic noncovalent interactions are strengthened with phosphorothioate analogs of DNA. These results clearly highlight the structure-directing role of the self-assembling organic species and strongly emphasize the significance of concentration, hydrophobicity, hydrogen-bonding, and pi-pi interactions of the artificial receptor in the formation of these noncovalent complexes. Because of the ability of DNA-binding compounds to influence gene expression, and therefore cell proliferation and differentiation, the interactions described above could be important in providing a better understanding of the mechanism of action of these noncovalent genetic regulators.

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Section: Methodssupporting

confidence: 78%

Characterization of specific noncovalent complexes between guanidinium derivatives and single-stranded DNA by MALDI

Ohara

Smietana

Vasseur

2006

J. Am. Soc. Mass Spectrom.

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“…All solvents and other reagents were purchased from commercial sources and used without further purification. The mono-Boc amines were synthesized from the commercially available diamines by using a literature procedure (10 equiv of diamine and 1 equiv of Boc 2 O in chloroform followed by an aqueous work up to remove unreacted diamine) (35 [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] (RQIKIWFQNRRMKWKK), and homopolymers of L-arginine (R5-R9) and D-arginine (r5-r9) were prepared with an automated peptide synthesizer (ABI433) by using standard solid-phase fluorenylmethoxycarbonyl (Fmoc) chemistry (36) with HATU as the peptide coupling reagent. The fluorescein moiety (Fl) was attached via an aminohexanoic acid spacer by treating a resin-bound peptide (1.0 mmol) with FITC (1.0 mmol) and diisopropyl ethyl amine (5 mmol) in dimethylformamide (DMF; 10 ml) for 12 h. Cleavage from the resin was achieved by using 95:5 trifluoroacetic acid (TFA)͞triisopropylsilane.…”

Section: Methodsmentioning

confidence: 99%

The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters

Wender

Mitchell

Pattabiraman

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

1,496

1,446

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Certain proteins contain subunits that enable their active translocation across the plasma membrane into cells. In the specific case of HIV-1, this subunit is the basic domain Tat49-57 (RKKRRQRRR). To establish the optimal structural requirements for this translocation process, and thereby to develop improved molecular transporters that could deliver agents into cells, a series of analogues of Tat49-57 were prepared and their cellular uptake into Jurkat cells was determined by flow cytometry. All truncated and alaninesubstituted analogues exhibited diminished cellular uptake, suggesting that the cationic residues of Tat49-57 play a principal role in its uptake. Charge alone, however, is insufficient for transport as oligomers of several cationic amino acids (histidine, lysine, and ornithine) are less effective than Tat49-57 in cellular uptake. In contrast, a 9-mer of L-arginine (R9) was 20-fold more efficient than Tat49-57 at cellular uptake as determined by Michaelis-Menton kinetic analysis. The D-arginine oligomer (r9) exhibited an even greater uptake rate enhancement (>100-fold). Collectively, these studies suggest that the guanidinium groups of Tat49-57 play a greater role in facilitating cellular uptake than either charge or backbone structure. Based on this analysis, we designed and synthesized a class of polyguanidine peptoid derivatives. Remarkably, the subset of peptoid analogues containing a six-methylene spacer between the guanidine head group and backbone (N-hxg), exhibited significantly enhanced cellular uptake compared to Tat49-57 and even to r9. Overall, a transporter has been developed that is superior to Tat49-57, protease resistent, and more readily and economically prepared.

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“…Compound 1 has been synthesized in a 80% yield by a previously published procedure and the analyses were in agreement with the literature [39]. Analytical data for 1: …”

Section: Synthesis Of Compoundmentioning

confidence: 99%

Organometallic 99mTc-technetium(I)- and Re-rhenium(I)-folate derivatives for potential use in nuclear medicine

Müller

Dumas

Hoffmann

et al. 2004

Journal of Organometallic Chemistry

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A Constrained Diketopiperazine as a New Scaffold for the Synthesis of Peptidomimetics

Cited by 35 publications

References 21 publications

Characterization of specific noncovalent complexes between guanidinium derivatives and single-stranded DNA by MALDI

Characterization of specific noncovalent complexes between guanidinium derivatives and single-stranded DNA by MALDI

The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters

Organometallic 99mTc-technetium(I)- and Re-rhenium(I)-folate derivatives for potential use in nuclear medicine

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