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[007]

Прошу помощи у уважаемых участников форума по поиску методов получения двух пептидов:

1. Pro-Pro-Gly

ProProGly.mol

2. pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2 (triptorelin), CAS 57773-63-4

triptorelin.mol

Заранее благодарен!

[Arkadii_Tarasevych]

Ссылки по второму веществу:

1. Method for preparing triptorelin by solid phase polypeptide synthesis method By Cui, Qi; Zhou, Yiming From Faming Zhuanli Shenqing (2009), CN 101357936 A 20090204. Language: Chinese, Database: CAPLUS
The method comprises (1) adopting Rink Amide AM resin or Rink Amide MBHA resin as raw material, sequentially linking protected amino acids (Gly, Pro, Arg(Pbf), Leu, D-Trp, Tyr(tBu), Ser(tBu), Trp, His(Trt), pGlu) at 10-60° to obtain protected decapeptide resin, removing Fmoc-protective group while deprotecting side chain; (2) cutting peptide from resin with TFA/EDT/H2O/TIS (800-680 mL: 35-18 mL: 35-18 mL: 10-3.7 mL) at 10-60° for 1-6 h to obtain crude product; (3) dissolving in acetic acid, purifying by C18 or C8 column chromatog. with 0.1-1 M acetate or phosphate or trifluoroacetic acid-acetonitrile(9-6:1-4) as mobile phase, freeze drying to obtain refined triptorelin product. The inventive method has advantages of stable process, easily available raw materials, short prodn. period, high yield, stable quality, low prodn. cost, high peptide-linking efficiency, no employment of toxic hydrogen fluoride, less three-waste pollution, high purifn. yield(over 25%), peptide-linking yield of over 98% in each step, peptide-cutting yield of 78.8% and total yield of 25.4%.
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2. Development of novel 68Ga- and 18F-labeled GnRH-I analogs with high GnRHR-targeting efficiency By Schottelius, Margret; Berger, Sebastian; Poethko, Thorsten; Schwaiger, Markus; Wester, Hans-Juergen From Bioconjugate Chemistry (2008), 19(6), 1256-1268. Language: English, Database: CAPLUS
A large majority of tumors of the reproductive system express the gonadotropin releasing hormone receptor (GnRHR). Blockade and activation of this receptor with various antagonistic and agonistic analogs of native GnRH-I (pGlu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly10-NH2), resp., has shown efficient suppression of tumor growth. In this study, the GnRH-receptor system has been evaluated with respect to its suitability as a target for in vivo peptide receptor targeting using radiolabeled GnRH-analogs, and in parallel, new 18F- and 68Ga-labeled GnRH analogs have been developed. In vitro radioligand binding assays performed with various GnRHR-expressing human cell lines using [125I]Triptorelin (D-Trp6-GnRH-I) as the std. radioligand revealed a very low level of GnRH receptor expression on the cell surface. Generally, total cellular activity was very low (∼3% of the applied activity), and only a small fraction (max. 40%) of cell-assocd. activity could be attributed to receptor-specific radioligand binding/internalization. However, substitution of fetal calf serum by NU serum in the culture medium led to increased and stable GnRHR-expression, esp. in the ovarian cancer cell line EFO-27, thus allowing for a stable exptl. setup for the evaluation of the new radiolabeled GnRH-I analogs. The new radiolabeled GnRH-I analogs developed in this study were all based on the D-Lys6-GnRH-I-scaffold. For 68Ga-labeling, the latter was coupled with DOTA at D-Lys6. To allow 18F-labeling via chemoselective oxime formation, D-Lys6-GnRH-I was also conjugated with Ahx (aminohexanoic acid) or β-Ala, which in turn was coupled with Boc-aminooxyacetic acid. 18F-labeling via oxime formation with 4-[18F]fluorobenzaldehyde was performed using the Boc-protected (Boc = tert-butoxycarbonyl) precursors. Receptor affinities of [68Ga]DOTA-GnRH-I, D-Lys6-Ahx([18F]FBOA)-GnRH-I, and D-Lys6-βAla([18F]FBOA)-GnRH-I (FBOA = fluorobenzyloxime acetyl) were detd. using GnRHR-membrane prepns., and internalization efficiency of the new radioligands was detd. in EFO-27 cells. Both quantities were highest for D-Lys6-Ahx([18F]FBOA)-GnRH-I (IC50 = 0.50 ± 0.08 nM vs 0.13 ± 0.08 nM for Triptorelin; internalization: 86 ± 16% of the internal ref. [125I]Triptorelin), already substantially reduced in the case of the -βAla([18F]FBOA)-deriv. (IC50 = 0.86 ± 0.13 nM; internalization: 42 ± 3% of [125I]Triptorelin), while the [68Ga]DOTA-analog showed almost complete loss of binding affinity and ligand internalization (IC50 = 13.3 ± 1.0 nM; internalization: 2.6 ± 1.0% of [125I]Triptorelin). Generally, the lipophilic residue [18F]FBOA is much better tolerated as a modification of the D-Lys6-side chain, with receptor affinity of the resp. analogs strongly depending upon spacer length between the D-Lys6-side chain and the [18F]FBOA-moiety. In summary, D-Lys6(Ahx-[18F]FBOA)-GnRH-I shows the highest potential for efficient GnRHR-targeting in vivo of the compds. investigated. Unfortunately, however, the very low cell surface expression of GnRH-receptors and thus very low radioligand uptake by GnRHR-pos. tumor cells found in vitro was also confirmed by a preliminary biodistribution study in OVCAR-3 xenografted nude mice using the std. GnRHR radioligand [125I]Triptorelin. Tumor uptake was lower than blood activity concn. at 1 h p.i. (0.49 ± 0.05 vs 0.96 ± 0.13 for tumor and blood, resp.). These data seriously challenge the suitability of the GnRHR-system as a suitable target for in vivo peptide receptor imaging using radiolabeled GnRH-I derivs., despite the availability of high-affinity radiolabeled receptor-ligands such as D-Lys6(Ahx-[18F]FBOA)-GnRH-I.
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3. Methods for production of peptide derivatives By Tovi, Avi; Eidelman, Chaim; Shushan, Shimon; Elster, Shai; Alon, Hagi; Ivchenko, Alexander; Butilca, Gabriel-Marcus; Zaovi, Gil; Alterman, Eleonora; Bar-Oz, Leah; et alFrom PCT Int. Appl. (2006), WO 2006119388 A2 20061109. Language: English, Database: CAPLUS
The invention relates to methods for the prepn. of peptide amide derivs. by a combination of solid-phase synthesis and post-assembly soln.-phase synthesis. The peptide C-terminal amide derivs. are further converted to peptide acetates. Examples describe the syntheses of leuprolide, goserelin,triptorelin and eptifibatide.
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4. Process for the synthesis of a peptide having a Trp residue By Jackson, Steven Allen From PCT Int. Appl. (2002), WO 2002051861 A2 20020704. Language: English, Database: CAPLUS
A process for the solid phase synthesis of peptides A1-A2-A3-Ser-A5-D-Trp-Leu-A8-Pro-Ala10-R1 [A1 = pGlu or N-Ac-D-β-Nal (β-Nal = β-1- or β-2-naphthylalanine); A2 = His, D-p-Cl(or F)-Phe; A3 = Trp or D-Trp; A5 = Tyr, NicLys (Nε-nicotinoyllysine), cPzACAla [cis-3-(4-pyrazinylcarbonylaminocyclohexyl)alanine], or PicLys (Nε-picolinoyllysine); A8 = Arg, hArgEt2 [N,N'-guanidino(diethyl)-homoarginine], hArg(Bu), hArg(CH2CF3), or Lys(iPr); A10 = Gly, D-Ala or is deleted; R1 = NH2 or NHEt] comprises temporarily protecting the indole ring of the tryptophan residue with a side chain protecting group which is labile to a base and removal of the protecting group during cleavage of the peptide from the solid support. The procedure was applied to the synthesis of pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2 ([D-Trp6]LHRH-NH2).

[Arkadii_Tarasevych]

По первому:

1. (9H-Fluoren-9-yl)methanesulfonyl (Fms): An Amino Protecting Group Complementary to Fmoc By Ishibashi, Yoshitaka; Miyata, Kengo; Kitamura, Masato From European Journal of Organic Chemistry (2010), (22), 4201-4204. Language: English, Database: CAPLUS
A sulfonamide-based protecting group (PG), (9H-fluoren-9-yl)methanesulfonyl (Fms), which can be used in a similar way to the well-established Fmoc PG, was developed. The advantages of this new PG were demonstrated in the successful formation of a phosphonamide between an N-Fms-protected α-phosphonoalanine monoester and secondary alkylamines, including (R)-2-phenylethylamine, (S)-phenylalanine tert-Bu ester (H-Phe-OtBu), H-Pro-Gly-OtBu, and H-Phe-Phe-OtBu, without formation of oxazaphospholine, which is a serious problem assocd. with the Fmoc PG. The success should pave the way to the solid-phase synthesis of unnatural peptides substituted with α-amino phosphonic acid (AP) at essentially any arbitrary position without significant modification of the Fmoc-based chem. that has been accumulated since Carpino's report in 1970. The N-Fms-AP monomer would attract much attention in the field of peptide mimetics.
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2. Investigating sequence space: how important is the spatial arrangement of functional groups in the asymmetric aldol reaction catalyst H-Pro-Pro-Asp-NH2? By Revell, Jefferson D.; Wennemers, Helma From Advanced Synthesis & Catalysis (2008), 350(7+8), 1046-1052. Language: English, Database: CAPLUS
H-Pro-Pro-Asp-NH2 1 is a versatile catalyst for asym. aldol reactions. Within the catalyst structure, both the N-terminal secondary amine and the carboxylic acid are crucial for efficient catalysis. Here, the importance of the arrangement of these two functional groups towards each other was examd. Several analogs of H-Pro-Pro-Asp-NH2 were prepd. in which the secondary amine and the carboxylic acid occupy different positions. Evaluation of their catalytic properties revealed that the placement of these two functional groups is highly crit. for efficient catalysis. Even seemingly small structural modifications, for example, one methylene group more or less, can modify the catalytic properties significantly. The results demonstrate the difficulty in rationally designing a peptidic catalyst and the value of combinatorial smart screening methods for catalyst discovery.
SubstancesReactions~12 Citings Full TextLink0 Comments 0 Tags

3. Catalytic removal of N-allyloxycarbonyl groups using the [CpRu(IV)(π-C3H5)(2-quinolinecarboxylato)]PF6 complex. A new efficient deprotecting method in peptide synthesis By Tanaka, Shinji; Saburi, Hajime; Murase, Takanori; Yoshimura, Masahiro; Kitamura, Masato From Journal of Organic Chemistry (2006), 71(12), 4682-4684. Language: English, Database: CAPLUS
A variety of amines including even sterically less demanding and highly nucleophilic secondary amines have been efficiently deprotected without decarboxylative N-allylation from the corresponding N-allyloxycarbonyl (N-AOC) compds. by using a catalytic amt. of [CpRu(IV)(π-C3H5)(2-quinolinecarboxylato)]PF6 in the presence of 1 M amt. of trifluoromethanesulfonic acid, the general utility of which has been demonstrated by the efficient synthesis of a collagen protein unit tripeptide, Pro-Pro-Gly.
SubstancesReactions~6 Citings Full TextLink0 Comments 0 Tags

4. An efficient synthesis of bradykinin cycloanalogs By Mutule, I.; Mutulis, F.; Erglis, D.; Jakstina, D.; Sekacis, I.; Rozite, S.; Grigor'eva, V. D.; Misina, I.; Cipens, G. From Bioorganicheskaya Khimiya (1988), 14(3), 299-307. Language: Russian, Database: CAPLUS
[Cyclo(9→1ε), Lys1, Gly6]bradykinin (I; X = null, Y = Gly) and cyclo-ε-kallidin (I; X = Arg, Y = Ser) were prepd. out by std. methods of peptide coupling using pentafluorophenyl esters. Fragment condensations were at the type (3 + 3 or 4) + 3.

[007]

Аркадий, спасибо! Я правда не знаю на сколько полная литература в Каплусе по сравнению с СФ.

[Arkadii_Tarasevych]

Всё было найдено по Скайфайндеру, я сам не знаю, почему везде пишется Каплус.