Miniaturized hemoproteins

Nastri, Flavia; Lombardi, Angela; D’Andrea, Luca Domenico; Sanseverino, Marina; Maglio, Ornella; Pavone, Vincenzo

doi:10.1002/(sici)1097-0282(1998)47:1<5::aid-bip3>3.3.co;2-t

Cited by 15 publications

(25 citation statements)

References 10 publications

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“…1 H NMR analyses indicate that two tolyl groups among the three tolyl groups of a porphyrin are high-field shifted by the ring current effect of the other porphyrin, which suggests a side-by-side arrangement of the porphyrins. The high-field shift and the signal line broadening are in the order toluene-d 8 4 CD 2 Cl 2 4 DMF-d 7 . The variable temperature NMR measurements in CD 2 Cl 2 indicate a dynamic process involving the porphyrins.…”

Section: Resultsmentioning

confidence: 97%

“…3(d)], with four sets of pyrrole protons and two sets of tolyl signals. The extremely broadened signals of 2d at 303 K are probably due to aggregation of the porphyrins in toluene-d 8 . No obvious spectrum change was observed when the concentration of 2d was varied from 1.0 to 4.0 mM at 303 K. However, no direct and clear evidence has been obtained yet on whether the porphyrins assemble in toluene intramolecularly or intermolecularly.…”

Section: (B)] Help Further Investigations On the Dynamic Processes (1)mentioning

confidence: 98%

“…In toluene-d 8 (2.0 mM), the 1 H NMR signals of 2d are extremely broadened at 303 K [ Fig. 4(a)] and, as a matter of fact, no information could be obtained from this spectrum.…”

Section: (B)] Help Further Investigations On the Dynamic Processes (1)mentioning

confidence: 99%

“…2(d) and 3(e), although the detailed structure of 2d is not yet clear because no single crystal has been obtained (for UV-vis and CD spectral results, see below). Comparing the 1 H NMR spectra of 2d in DMF-d 7 , CD 2 Cl 2 and toluene-d 8 (Figs. 2-4), the signal width becomes broader in the order DMF-d 7 o CD 2 Cl 2 o toluene-d 8 (at both 303 and 353 K).…”

Section: (B)] Help Further Investigations On the Dynamic Processes (1)mentioning

confidence: 99%

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Spectroscopic characterization of an assembled pair of free-base and zinc porphyrins linked by the cyclic ?-sheet peptide Gramicidin SElectronic supplementary information (ESI) available: complete synthetic details and characterization of the GS derivatives. See http://www.rsc.org/suppdata/nj/b4/b402541e/

et al. 2004

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A pair of porphyrins was linked to the Orn side chains of Gramicidin S [cyclo(-D-Phe-Pro-Val-Orn-Leu-) 2 ] and its derivatives via the amide bonds; the assorted porphyrins were characterized by various spectroscopic methods. The high-field shifts of the porphyrin signals in the 1 H NMR spectrum and the exciton-coupled Cotton effects in the CD spectrum of cyclo[-D-Phe-Pro-Val-Orn(Por)-Leu-] 2 are both intense compared to those of cyclo[-D-Phe-Pro-Val-Dab(Por)-Leu-] 2 or cyclo[-D-Phe-Pro-Val-Lys(Por)-Leu-] 2 (Dab, diaminobutyric acid; Por, the side-chain linked porphyrin). Some 1 H NMR signals of the tolyl protons of the porphyrins coalesce at 353 K in CD 2 Cl 2 , which reveals dynamic processes of the porphyrins. The intensities of the Cotton effect are: Gramicidin S with a pair of free-base porphyrins E Gramicidin S with a free-base porphyrin and a zinc porphyrin o Gramicidin S with a pair of zinc porphyrins. The 1 H NMR, UV-vis, CD and fluorescence spectra show that the solvent substantially influences the assembly of the porphyrins. These spectroscopic studies suggest that the strength of the intramolecular interactions between a pair of porphyrins is in the order of toluene 4 CH 2 Cl 2 4 DMF.{ Electronic supplementary information (ESI) available: complete synthetic details and characterization of the GS derivatives. See

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Section: Resultsmentioning

confidence: 97%

Section: (B)] Help Further Investigations On the Dynamic Processes (1)mentioning

confidence: 98%

“…In toluene-d 8 (2.0 mM), the 1 H NMR signals of 2d are extremely broadened at 303 K [ Fig. 4(a)] and, as a matter of fact, no information could be obtained from this spectrum.…”

Section: (B)] Help Further Investigations On the Dynamic Processes (1)mentioning

confidence: 99%

Section: (B)] Help Further Investigations On the Dynamic Processes (1)mentioning

confidence: 99%

See 2 more Smart Citations

Spectroscopic characterization of an assembled pair of free-base and zinc porphyrins linked by the cyclic ?-sheet peptide Gramicidin SElectronic supplementary information (ESI) available: complete synthetic details and characterization of the GS derivatives. See http://www.rsc.org/suppdata/nj/b4/b402541e/

et al. 2004

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“…Then, we attempted to reproduce the active‐site complexity in a de novo designed small protein by also using our achievements in the class of artificial diiron oxo13a, 27 and heme models 8b. 28…”

Section: Discussionmentioning

confidence: 99%

De Novo Design, Synthesis and Characterisation of MP3, A New Catalytic Four‐Helix Bundle Hemeprotein

Faiella

Maglio

Nastri

et al. 2012

Chemistry A European J

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A new artificial metalloenzyme, MP3 (MiniPeroxidase 3), designed by combining the excellent structural properties of four-helix bundle protein scaffolds with the activity of natural peroxidases, was synthesised and characterised. This new hemeprotein model was developed by covalently linking the deuteroporphyrin to two peptide chains of different compositions to obtain an asymmetric helix-loop-helix/heme/helix-loop-helix sandwich arrangement, characterised by 1) a His residue on one chain that acts as an axial ligand to the iron ion; 2) a vacant distal site that is able to accommodate exogenous ligands or substrates; and 3) an Arg residue in the distal site that should assist in hydrogen peroxide activation to give an HRP-like catalytic process. MP3 was synthesised and characterised as its iron complex. CD measurements revealed the high helix-forming propensity of the peptide, confirming the appropriateness of the model procedure; UV/Vis, MCD and EPR experiments gave insights into the coordination geometry and the spin state of the metal. Kinetic experiments showed that Fe(III)-MP3 possesses peroxidase-like activity comparable to R38A-hHRP, highlighting the possibility of mimicking the functional features of natural enzymes. The synergistic application of de novo design methods, synthetic procedures, and spectroscopic characterisation, described herein, demonstrates a method by which to implement and optimise catalytic activity for an enzyme mimetic.

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Branched porphyrins as functional scaffolds for multisite bioconjugation

Engelen

Lombardi

Vitale

et al. 2014

Biotech and App Biochem

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Bioconjugation is a rapidly expanding field because of the numerous potential applications of bioconjugate materials. We explored the usefulness of branched porphyrins as rigid scaffolds, bearing multiple sites for bioconjugation. To this end, we first selected the tetrakis(p-[aminomethyl] phenyl) porphyrin (TAMPP) macrocycle and developed a straightforward synthetic protocol, able to provide the desired tetraphenylporphyrin, carrying four functional amino groups. The partially protection of the amino groups by tert-butoxy-carbonyl allowed the selective and specific decoration of the porphyrin with different peptide sequences. To explore the utility of the macrocycle as molecular scaffold for bioconjugation, we selected peptide sequences able to function as thrombin inhibitors. In particular, two peptide sequences, named CS3 and ES7, able to interact, respectively, with the thrombin catalytic site and the fibrinogen recognition exosite, were joined onto the porphyrin macrocycle, providing the multisite-directed inhibitor CS3-TAMPP-ES7. This multisite inhibitor and its Mn(III) complex are able to inhibit α-thrombin-catalyzed hydrolysis of Tos-Gly-Pro-Arg-nitroanilide with inhibition constants in the micromolar range, as well as the hydrolysis of the natural substrate fibrinogen. The inhibitor is resistant against enzymatic degradation by thrombin and is highly selective. The Mn(III) complex is capable of interacting with clot-bound thrombin and partially inhibits clot growth in the presence of fibrinogen. The results herein reported are very promising, suggesting the potential of the newly developed conjugate as new imaging agents for clot detection.

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Miniaturized hemoproteins

Cited by 15 publications

References 10 publications

De Novo Design, Synthesis and Characterisation of MP3, A New Catalytic Four‐Helix Bundle Hemeprotein

Branched porphyrins as functional scaffolds for multisite bioconjugation

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