Monitoring the Chemical Assembly of a Transmembrane Bradykinin Receptor Fragment: Correlation Between Resin Solvation, Peptide Chain Mobility, and Rate of Coupling

Oliveira, Eliandre de; Cilli, Eduardo Maffud; Miranda, Antônio; Jubilut, Guita Nicolaewsky; Alberício, Fernando; Andreu, David; Paiva, Antonio Cechelli de Mattos; Schreier, Shirley; Tominaga, Mineko; Nakaie, Clóvis R.

doi:10.1002/1099-0690(200211)2002:21<3686::aid-ejoc3686>3.0.co;2-5

Cited by 30 publications

(23 citation statements)

References 14 publications

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“…In these works, we have hypothesized that the 1:1 sum of Gutman's [5] electron acceptor number (AN) and electron donor number (DN) numbers would be a dimensionless, accurate polarity term. Due to the presence of opposing concepts within the same parameter, the (AN+DN) term was denoted an amphoteric constant or scale [6]. The application of this novel polarity constant can facilitate the prediction of polymer or peptide-polymer solvation, thereby improving techniques such as solid-phase peptide synthesis [7][8][9].…”

Section: Introductionsupporting

confidence: 64%

Application of Electron Paramagnetic Resonance Spectroscopy for Validation of the Novel (AN+DN) Solvent Polarity Scale

Malavolta

Poletti

Silva

et al. 2008

IJMS

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Abstract:Based on solvation studies of polymers, the sum (1:1) of the electron acceptor (AN) and electron donor (DN) values of solvents has been proposed as an alternative polarity scale. To test this, the electron paramagnetic resonance isotropic hyperfine splitting constant, a parameter known to be dependent on the polarity/proticity of the medium, was correlated with the (AN+DN) term using three paramagnetic probes. The linear regression coefficient calculated for 15 different solvents was approximately 0.9, quite similar to those of other well-known polarity parameters, attesting to the validity of the (AN+DN) term as a novel "two-parameter" solvent polarity scale.

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Section: Introductionsupporting

confidence: 64%

Application of Electron Paramagnetic Resonance Spectroscopy for Validation of the Novel (AN+DN) Solvent Polarity Scale

Malavolta

Poletti

Silva

et al. 2008

IJMS

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“…In the following years, the literature was filled with reports on successful stepwise SPPS at 60 °C or higher temperatures by using conventional heating and microwaves , manual microwave‐assisted stepwise SPPS using 60 °C as the set temperature , microwave‐assisted on‐bead disulfide bond formation using 60 °C as the set temperature and peptide detachment from resin/full deprotection at 45–50 °C using conventional and microwave heating . As regards to the diffusion factor, it is consensual that in traditional SPPS (peptide assembly on resin at room temperature), some solvents and their binary mixtures are able to provide effective swelling of peptide resins, enhancing diffusion of the incoming activated amino acids through their pores and, therefore, facilitating intermolecular and intramolecular chemical reactions . The mixture 20% DMSO/NMP, used in the present study and fully stable at 60 °C, is among the binary mixtures of aprotic solvents known to have this capacity, which we could confirm by observing higher solvation degrees of the peptide‐MBHA studied than in DMF (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Synthesis and properties of cyclic gomesin and analogues

Machado¹,

Fázio²,

Miranda

et al. 2012

Journal of Peptide Science

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Gomesin (Gm) was the first antimicrobial peptide (AMP) isolated from the hemocytes of a spider, the Brazilian mygalomorph Acanthoscurria gomesiana. We have been studying the properties of this interesting AMP, which also displays anticancer, antimalarial, anticryptococcal and anti-Leishmania activities. In the present study, the total syntheses of backbone-cyclized analogues of Gm (two disulfide bonds), [Cys(Acm)(2,15)]-Gm (one disulfide bond) and [Thr(2,6,11,15),(D)-Pro(9)]-Gm (no disulfide bonds) were accomplished, and the impact of cyclization on their properties was examined. The consequence of simultaneous deletion of pGlu(1) and Arg(16) -Glu-Arg(18) -NH(2) on Gm antimicrobial activity and structure was also analyzed. The results obtained showed that the synthetic route that includes peptide backbone cyclization on resin was advantageous and that a combination of 20% DMSO/NMP, EDC/HOBt, 60 °C and conventional heating appears to be particularly suitable for backbone cyclization of bioactive peptides. The biological properties of the Gm analogues clearly revealed that the N-terminal amino acid pGlu(1) and the amidated C-terminal tripeptide Arg(16) -Glu-Arg(18) -NH(2) play a major role in the interaction of Gm with the target membranes. Moreover, backbone cyclization practically did not affect the stability of the peptides in human serum; it also did not affect or enhanced hemolytic activity, but induced selectivity and, in some cases, discrete enhancements of antimicrobial activity and salt tolerance. Because of its high therapeutic index, easy synthesis and lower cost, the [Thr(2,6,11,15),(D)-Pro(9)]-Gm analogue remains the best active Gm-derived AMP developed so far; nevertheless, its elevated instability in human serum may limit its therapeutic potential.

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“…Due to the coexistence of two opposite conceptual physicochemical terms, this novel polarity scale was recently designated amphoteric. 27 The volume of solvated bead (in percentage) occupied by each solvent system was selected as swelling parameter to monitor solvation capacity of resin batches in ionized and nonionized forms.…”

Section: Swelling Degree Of Bharmentioning

confidence: 99%

Use of the same polymer for synthesis and purification of peptides

Silva¹,

Etchegaray²,

Carvalho³

et al. 2005

J. Braz. Chem. Soc.

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Este trabalho revela uma estratégia biotecnológica incomum mas valiosa e relacionada com o uso de um mesmo polímero (benzidrilamino-resina, BHAR) para fins de síntese e purificação por troca aniônica de peptídeos. Inicialmente, o octapeptídeo DRVYIHPF-NH 2 foi sintetizado em BHAR com 1% e 3% de intercruzamento e contendo 2,5 mmol g -1 de grupos amônio. Devido certamente a uma menor rigidez da sua estrutura polimérica, um maior rendimento na síntese (cerca de 80%) foi obtido com a primeira resina. A seguir, os peptídeos DEVYEHPF-NH 2 e DEVYEDPF-NH 2 carregados negativamente (-1 e -3 em pH neutro, respectivamente), ambos sintetizados em 1% BHAR, foram submetidos a um teste de separação cromatográfica no mesmo tipo de resina (1% e 3%). Concordante com resultados da síntese de peptídeos e de valores de inchamento dos grãos das resinas, obtidos por microscopia, uma melhor separação entre ambos os peptídeos ocorreu com o lote de 1% BHAR. Estes achados demonstraram que a BHAR, aplicada até o momento somente para a síntese peptídica, se contiver elevado teor de grupos amônio positivos, pode ser utilizada alternativamente como suporte sólido para purificação cromatográfica deste tipo de molécula biológica.This work reveals an uncommon but valuable biotechnological approach regarding the use of a same polymer (benzhydrylamine-resin, BHAR) for synthesis and anion exchange purification of peptides. Initially, the octapeptide DRVYIHPF-NH 2 was synthesized in 1% and 3% cross-linked BHAR, attaching 2.5 mmol g -1 ammonium groups. Due certainly to its less rigid polymeric backbone, higher synthesis yield (about 80%) was achieved with the former resin. Next, the negatively charged peptides DEVYEHPF-NH 2 and DEVYEDPF-NH 2 (-1 and -3 in neutral pH, respectively), both synthesized in 1% BHAR were submitted to chromatographic separation test in this same type of resin (1% and 3%). Following comparative results of peptide synthesis and swelling data of resin beads obtained by microscopy, an improved separation of both peptides occurred with 1% BHAR batch. These findings demonstrated that BHAR applied so far for peptide synthesis, when containing high amount of positively charged ammonium groups, can be also used alternatively as a solid support for chromatographic purification of this type of biological molecule.Keywords: peptide synthesis, resin, anion exchange chromatography, polymer, solvent polarity IntroductionThe inception of solid phase peptide synthesis (SPPS) 1 almost four decades ago 2 represented a landmark in the use of cross-linked beaded polymers, which were, until that time, restricted to stationary phases in column chromatography. Since then, various studies have been conducted in order to develop more varied applications for such polymeric materials. In addition to the peptide synthesis method itself, the concept of performing chemical reactions on an insoluble polymeric structure has, for instance, been successfully extended to oligonucleotides 3 and polysaccharides. 4 In recent years, a process denoted solid phase o...

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Monitoring the Chemical Assembly of a Transmembrane Bradykinin Receptor Fragment: Correlation Between Resin Solvation, Peptide Chain Mobility, and Rate of Coupling

Cited by 30 publications

References 14 publications

Application of Electron Paramagnetic Resonance Spectroscopy for Validation of the Novel (AN+DN) Solvent Polarity Scale

Application of Electron Paramagnetic Resonance Spectroscopy for Validation of the Novel (AN+DN) Solvent Polarity Scale

Synthesis and properties of cyclic gomesin and analogues

Use of the same polymer for synthesis and purification of peptides

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