Chromium complexes peptides

H. A. Headlam and P. A. Lay, EPR spectroscopic studies of the reduction of chromium(VI) by methanol in the presence of peptides. Formation of long-lived chromium(V) peptide complexes, Inorg. Chem., 40 (2001) 78-86. 

X 10 M s and was 3.1 x 10 M s" at 25°C, pH 7.0 and ionic strength of 1.0 . Kinetic data was interpreted in terms of a mechanism of electron transfer from chromium(II) involving attack of Cr(II) adjacent to the Fe(III) center Analysis of the one-to-one chromium(III) cytochrome c complex revealed that the chromium(III) cross-linked two peptide fragments located in the heme.crevice by binding to tyrosine 67 and asparagine 52 The chromium(III) bound to reduced cytochrome c did not affect the ability of the protein to be reoxidized with ferricyanide and then to be reduced with dithionite . The chromium complex was oxidized by cytochrome oxidase at the same rate as the untreated ferrocytochrome c, however, the rate of reduction of the chromium complex by bovine heart submitochondrial particles was slower than that of untreated ferricytochrome c Thus, the binding of chromium(III) to cytochrome c appears to selectively inhibit its function in certain electron transfer reactions. 

Gez S, Luxenhofer R, Levina A, Codd R, Lay PA. 2005. Chromium(V) complexes of hydroxamic acids formation, structures, and reactivities. Inorg Chem 44(8) 2934—2943. Barnard PJ, Levina A, Lay PA. 2005. Chromium(V) peptide complexes sjmthesis and spectroscopic characterization. Inorg Chem 44(4) 1044-1053. 

Carreras CW, Pieper R, Khosla C (1997) The Chemistry and Biology of Fatty Acid, Polyketide, and Nonribosomal Peptide Biosynthesis. 188 85-126 Ceulemans A (1994) The Doublet States in Chromium (III) Complexes. A Shell-Theoretic View. 171 27-68... 

A further example shows that one may add more amino acids to an amino acid ester -earbene complex by employing the customary methods of peptide chemistry (64). Starting from pentacarbonyl[GlyOMe (phenyl) -earbene]chromium(0) and using the. V-hydroxysuccinimide/dicyclohexyl-carbodiimide) (NHS/DCCD) method, we succeeded in synthesizing the sequence 14 to 17 of human proinsulin C-peptide (Scheme 3). 

Dillon CT, Lay PA, Bonin AM, et al. 1993. In vitro DNA damage and mutations induced by a macrocyclic tetraamide chromium(V) complex implications for the role of Cr(V) peptide complexes in chromium-induced cancers. Carcinogenesis 14(9) 1875-1880. 

Scheme 8.4 Stepwise synthesis of the tetrapeptide 18, containing the sequence 14-17 of the human proinsulin C-peptide, from the methoxy(phenyl)carbene complex 16 via the carbene chromium derivative 17 as the intermediate (Gly-OMe and Pro-OMe were the methyl esters of glycine and proline). The C—N coupling reactions in steps (1)—(4) were carried out using the DCCD/HOSU method, explained in [35]...

L. S. Hegedus, Synthesis of Amino Acids and Peptides Using Chromium Carbene Complex Photochemistry, Acc. Chem. Res. 28, 299-305 (1995). 

A prerequisite for CTL-mediated immune response is the formation of the MHC-class I-peptide complex and subsequent recognition by the T-cell repertoire, which can be analyzed in cell lysis assays with MCr-loaded target cells. Chromium release is a measure for peptide-induced cell lysis by CTL, and indicates the potency of the peptide to serve as an allele-specific epitope. A synthetic epitope has been identified with the peptide library approach to elucidate the molecular basis for the observed cross-recognition of two ligands by a single receptor [53]. 

Abstract Planar-chiral ri -arene-Cr(CO)3 complexes represent highly valuable buUdlng blocks for the dlastereo- and enantloselectlve synthesis of complex natural products and related bloactlve compounds. Highly original and competitive overall syntheses of various classes of natural products, such as sesquiterpenes, diterpenes, alkaloids and compounds with axial chirality, have been developed. In certain cases, the whole strategy is based on arene chromium chemistry and the various chemical and stereochemical effects of the metal unit are exploited In several subsequent transformations. Cationic Cp-ruthenium complexes allow arylether formation by Sj Ar reactions and have found application in the synthesis of glyco-peptide antibiotics. 

Another applieation of photogenerated metal coordinated ketenes is based on the addition of protie nucleophiles and has been exploited in the synthesis of amino aeids and peptides. [66] As usual, the reactive intermediate is generated by photolysis of an aminoearbene complex 46, which may be a-alkylated in a previous step. The oxazolidine auxiliary applied successfully inducing asymmetry in the P-laetam formation, allowed an enantioselective synthesis of amino aeids. Sinee both enantiomers of the auxiliary may be obtained from the corresponding phenyl glycine enantiomer, natural (5) and non-natural R) amino acid esters 47 are accessible via this route (Scheme 25). A recent review on synthetical applications of chromium carbene photochemistry has been published, [li]... 

Aminolysis of methoxy carbene metal pentacarbonyl complexes of the chromium group yields amino carbene compounds. If the aminolysis is performed with amino acid esters, amino carbene derivatives of amino acids are obtained [162,163]. The metal carbene is relatively stable under a variety of conditions but can be removed with TFA. It may therefore be regarded as an amino protecting group in peptide synthesis. The metal amino carbene amino acid may be activated and coupled to other amino acid esters. Following this idea, Weiss and Fischer prepared various dipeptides, the tripeptide (OC)5Cr(Ph)-Ala-Ala-Ala-OMe 69 [162] and the tetrapeptide (OC)5Cr(Ph)-Gly-Gly-Pro-Gly-OMe 70 (Scheme 5.35) [163]. Treatment with cone. TFA at 20 °C for 10 min. removes the metal carbene group and furnishes the free peptide esters along with Cr(CO)g. Removal of the metal carbene is also possible with 80% acetic acid (80 °C, 30 min.), which leaves Boc... 

Hegedus, L.S. (1995) Synthesis of amino adds and peptides using chromium carbene complex photochemistry. Accounts of Chemical Research, 28, 299-305, and references therein. 

Pull993 Pulley, S.R. and Hegedus, L.S., Solid-Phase, Solution and Segment Condensation Peptide Syntheses Incorporating Chromium Carbene Complex-Derived Nonproteinogenic ( Unnatural ) Amino Acid Fragments, J. Am. Chem. Soc., 115 (1993) 9037-9047. 

Apart from aminolysis and olefin metathesis the photoactivation of aminocar-bene complexes offers another nonconventional entry into peptide synthesis. Irradiation into the hypsochromic MLCT-band of chromium aminocarbenes such as 201 generates a ketene-like intermediate 204 that is trapped by amino acid esters such as 202 or 205 to produce dipeptides 203 or 206 after enantioselective protonation (Scheme 11.49) [106]. This photochemical protocol generally combines good yields with high diastereoselectivities and is especially attractive for the incorporation of a-alkyl a-amino acid esters into peptides that may be hampered in conventional peptide synthesis methodologies due to steric hindrance [106c]. 

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