216774-45-7Relevant academic research and scientific papers
Synthesis and evaluation of the sensitivity and vibrational lifetimes of thiocyanate and selenocyanate infrared reporters
Levin, Daniel E.,Schmitz, Andrew J.,Hines, Shawn M.,Hines, Kevin J.,Tucker, Matthew J.,Brewer, Scott H.,Fenlon, Edward E.
, p. 36231 - 36237 (2016)
Two novel 2′-deoxyadenosine (dA) analogues, Si2-dA-SCN and Si2-dA-SeCN, and two novel phenylalanine (Phe) analogues, Boc-Me-PheCH2SCN and Boc-Me-PheCH2SeCN, have been synthesized and the thiocyanate (SCN) and selenocyanate (SeCN) functional groups evaluated as vibrational reporters. The syntheses of Si2-dA-SCN and Si2-dA-SeCN were accomplished in three steps in 16% and 32% overall yields, respectively, and the syntheses of Boc-Me-PheCH2SCN and Boc-Me-PheCH2SeCN were completed in four steps in 8.9% and 2.3% overall yields, respectively. The SCN and SeCN stretch vibrational modes were shown to be sensitive to the local environment by frequency shifts and full-width half-maximum (fwhm) changes in response to tetrahydrofuran (THF) and THF/water solvent mixtures. The vibrational lifetimes of the Si2-dA-SeCN (237 ± 12 ps) and Boc-Me-PheCH2SeCN (295 ± 31 ps) in THF solution were determined by ultrafast infrared pump-probe spectroscopy to be 1.5 to 3 times longer than those for Si2-dA-SCN (140 ± 6 ps) and Boc-Me-PheCH2SCN (102 ± 4 ps). The longer lifetimes for the SeCN analogues were attributed to the better insulating effects of the heavier selenium atom compared to the sulfur atom. The solvent sensitivity and longer vibrational lifetimes compared to other vibrational reporters suggest that SCN and SeCN vibrational reporters are well suited to studying several dynamic processes including protein and nucleic acid hydration and conformational changes, however stability issues may require post-synthetic modification methods to incorporate these reporters into biomacromolecules.
COMPOSITIONS CONTAINING, METHODS INVOLVING, AND USES OF NON-NATURAL AMINO ACIDS AND POLYPEPTIDES
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Paragraph 0593, (2016/07/27)
Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one oximine, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.
Stabilized 111In-labeled sCCK8 analogues for targeting CCK2-receptor positive tumors: Synthesis and evaluation
Roosenburg, Susan,Laverman, Peter,Joosten, Lieke,Eek, Annemarie,Oyen, Wim J. G.,De Jong, Marion,Rutjes, Floris P. J. T.,Van Delft, Floris L.,Boerman, Otto C.
experimental part, p. 663 - 670 (2011/02/25)
Radiolabeled cholecystokinin-8 (CCK8) peptide analogues can be used for peptide receptor radionuclide imaging and therapy for tumors expressing CCK2/gastrin receptors. Earlier findings indicated that sulfated CCK8 (sCCK8, Asp-Tyr(OSO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) may have better characteristics for peptide receptor radionuclide therapy (PRRT) than gastrin analogues. However, sCCK8 contains an easily hydrolyzable sulfated tyrosine residue and two methionine residues which are prone to oxidation. Here, we describe the synthesis of stabilized sCCK8 analogues, resistant to hydrolysis and oxidation. Hydrolytic stability was achieved by replacement of the Tyr(OSO3H) moiety by a robust isosteric sulfonate, Phe(p-CH 2SO3H). Replacement of methionine by norleucine (Nle) or homopropargylglycine (HPG) avoided undesired oxidation side-reactions. The phenylalanine analogue Phe(p-CH2SO3H) of l-tyrosine, synthesized by a modification of known synthetic routes, was incorporated in three peptides: sCCK8[Phe2(p-CH2SO3H),Met 3,6], sCCK8[Phe2(p-CH2SO3H),Nle 3,6], and sCCK8[Phe2(p-CH2SO 3H),HPG3,6]. All peptides were N-terminally conjugated with the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-N,N,N,N- tetraacetic acid) and radiolabeled with In-111. In vitro binding assays on CCK2R-expressing HEK293 cells revealed that all three peptides showed specific binding and receptor-mediated internalization, with binding affinity values (IC50) in the nanomolar range. In vitro oxidation studies demonstrated that peptides with Nle or HPG indeed were resistant to oxidation. In vivo targeting studies in mice with AR42J tumors showed that tumor uptake was highest for 111In-DOTA-sCCK8 and 111In-DOTA- sCCK8[Phe2(p-CH2SO3H),Nle3,6] (4.78 ± 0.64 and 4.54 ± 1.15%ID/g, respectively, 2 h p.i.). The peptide with the methionine residues replaced by norleucine (111In-DOTA- sCCK8[Phe2(p-CH2SO3H), Nle3,6]) showed promising in vivo characteristics and will be further investigated for radionuclide imaging and therapy of CCK2R-expressing tumors.
Negishi cross-coupling reactions of α-amino acid-derived organozinc reagents and aromatic bromides
Oswald, Claire L.,Carrillo-Márquez, Tomás,Caggiano, Lorenzo,Jackson, Richard F.W.
, p. 681 - 687 (2008/09/16)
The Negishi cross-coupling reaction of organozinc iodides derived from α-amino acids with aromatic bromides to give substituted phenylalanine derivatives is described, using either Pd(OAc)2 or Pd2(dba)3 in combination with P(o-Tol)3 as catalyst in DMF at 50 °C. Similar results are obtained using Pd[PtBu3]2 as catalyst. The difference in reactivity displayed between aryl iodides and bromides (ArI>ArBr) has been utilised in a short synthesis of an unsymmetrical, orthogonally protected para-phenylene bis-alanine derivative.
Synthesis of novel chiral amino acids possessing a porphyrin moiety
Tamiaki, Hitoshi,Onishi, Motoki
, p. 1029 - 1032 (2007/10/03)
Phenylalanine derivatives bearing a porphyrin moiety at the para- position were prepared in an enantiomerically pure form. The synthetic nonnatural aromatic amino acid reacted with amines and acids to give novel functionalized peptides without loss of the
An improved preparation of 4-hydroxymethyl-L-phenylalanine
Morera, Enrico,Ortar, Giorgio,Varani, Aurelio
, p. 4279 - 4285 (2007/10/03)
Palladium-catalyzed hydroformylation of methyl esters of N-Boc-L- tyrosine triflate (1a) and N-Boc-4-iodo-L-phenylalanine (1b) followed by reduction with sodium borohydride and standard deprotection procedures affords the title compound in 77 and 83% over
