Synthesis of<scp>l</scp>-2,3-<i>trans</i>-3,4-<i>cis-</i>Dihydroxyproline Building Blocks for Peptide Synthesis

Weir, Claudette A.; Taylor, Carol M.

doi:10.1021/jo982009d

Cited by 24 publications

(17 citation statements)

References 15 publications

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“…The material from this peak has a molecular mass of 283 Da, which perfectly matches the mass of the PTC-dihydroxyproline. Indeed, in mass spectrometric analysis the 283-Da component exhibited the same fragmentation pattern as authentic PTC-derivatized L-2,3-trans-3,4-cis-dihydroxyproline 3 (20,21). Dihydroxyproline is a very rare amino acid in biology (22), yet it was identified 35 years ago from acid hydrolysates of diatom biosilica (23).…”

Section: Tpsil1h and -2h Represent Higher Molecular Mass Isoforms Of mentioning

confidence: 99%

Silica Morphogenesis by Alternative Processing of Silaffins in the Diatom Thalassiosira pseudonana

Poulsen

Kröger

2004

Journal of Biological Chemistry

242

364

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For almost 200 years scientists have been fascinated by the ornate cell walls of the diatoms. These structures are made of amorphous silica, exhibiting species-specific, mostly porous patterns in the nano-to micrometer range. Recently, from the diatom Cylindrotheca fusiformis unusual phosphoproteins (termed silaffins) and long chain polyamines have been identified and implicated in biosilica formation. However, analysis of the role of silaffins in morphogenesis of species-specific silica structures has so far been hampered by the difficulty of obtaining structural data from these extremely complex proteins. In the present study, the five major silaffins from the diatom Thalassiosira pseudonana (tpSil1H, -1L, -2H, -2L, and -3) have been isolated, functionally analyzed, and structurally characterized, making use of the recently available genome data from this organism. Surprisingly, the silaffins of T. pseudonana and C. fusiformis share no sequence homology but are similar regarding amino acid composition and posttranslational modifications. Silaffins tpSil1H and -2H are higher molecular mass isoforms of tpSil1L and -2L, respectively, generated in vivo by alternative processing of the same precursor polypeptides. Interestingly, only tpSil1H and -2H but not tpSil1L and -2L induce the formation of porous silica patterns in vitro, suggesting that the alternative processing event is an important step in morphogenesis of T. pseudonana biosilica.During evolution many organisms (e.g. diatoms, sponges, radiolaria) have acquired the ability to use the ubiquitous monosilicic acid Si(OH) 4 for the formation of species specifically structured, silica-based exo-or endoskeletons (1). This interesting biomineralization phenomenon is mediated by cellular organic (macro-) molecules that accelerate silicic acid polycondensation and control morphogenesis of the forming silica (2). Diatoms are an extremely large group (Ͼ10,000 species) of unicellular eukaryotic algae that play a major role in biological silica cycling. Within the last few years diatom biosilica-associated proteins (termed silaffins) and long chain polyamines (LCPA) 1 have been identified and hypothesized to represent key components of the diatom biosilica-forming machinery. Silaffins and LCPA exhibit the remarkable ability to induce rapid silica deposition in vitro and to control the nanostructure of the forming silica (3). Therefore, unraveling the correlations between chemical structures, physical properties, and silica-forming activities of silaffins and LCPA will be important for understanding the molecular mechanism of species-specific biosilica nanopatterning. So far, silaffins have only been characterized from the diatom Cylindrotheca fusiformis. They are highly modified proteins/peptides rich in hydroxyamino acids (serine, threonine, hydroxyproline) and lysine residues. Silaffins natSil1A and -1B are O-phosphorylated at numerous sites and contain polyamine-modified lysine residues, features that enable these peptides to rapidly form silica nanospheres in vitr...

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Section: Tpsil1h and -2h Represent Higher Molecular Mass Isoforms Of mentioning

confidence: 99%

Silica Morphogenesis by Alternative Processing of Silaffins in the Diatom Thalassiosira pseudonana

Poulsen

Kröger

2004

Journal of Biological Chemistry

242

364

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“…3aR,4S,6aS)-5-(((9H-Fluoren-9-yl)methoxy)carbonyl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo [4,5-c]pyrrole-4-carboxylic Acid (9). 35 Compound 8 (1.82 g, 8.12 mmol, 1.0 equiv) was dissolved in 10% Na 2 CO 3aq (12.5 mL), and FmocCl (2.31 g, 8.93 mmol, 1.1 equiv) was added in 1,4-dioxane (12.5 mL). After being stirred for 16 h, the mixture was washed with Et 2 O (3 × 25 mL).…”

Section: ■ Conclusionmentioning

confidence: 99%

Scaling the Amphiphilic Character and Antimicrobial Activity of Gramicidin S by Dihydroxylation or Ketal Formation

et al. 2017

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The acid lability of aliphatic ketals, which often serve as protection groups for 1,2-diols, is influenced by their local structural environment. The acetonide of the protected amino acid cis-dihydroxyproline (Dyp) is a typical protecting group cleavable by traces of TFA. The tricyclic acetonide of the dipeptide d-Hot═Tap is resistant to TFA and thus can serve as a bioorthogonal modification of bioactive peptides. With the aim of improving antimicrobial activity and hemolytic properties, we use these reactivity differences to scale the membrane affinity of the decapeptide Gramicidin S cyclo(d-Phe-Pro-Val-Orn-Leu-) (GS). The cis-dihydroxylated amino acids are used to increase the polarity of GS or obversely decrease the polarity by stereoselective ketal formation with an aliphatic ketone. While Dyp (GS mimetic 15) has only minimal influence on the biological properties of GS, d-Hot═Tap at the position of d-Phe1-Pro2 eradicates the biological activity (GS mimetic 16). The acid-stable ketals 17-19 are bioorthogonal modifications which reconstitute the biological activity of GS. We describe an improved synthesis of orthogonally protected Fmoc-Dyp-acetonide (9) and of several Fmoc-d-Hot═Tap-ketals for solid-phase peptide synthesis.

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“…Dhp saved two reaction steps because Dyp as a starting point for the assembly of CMP 12 would require a diol protecting group during peptide coupling. 16 Additionally, Dhp is preferred over Dyp in SPPS because of the poor nucleophilicity of the secondary amine of Dyp, resulting in poor acylation yields and long reaction times. 17 The osmate-mediated dihydroxylation of olefins invented by Criegee has undergone significant improvements in the last decades.…”

mentioning

confidence: 99%

“…The double bond in CMP 5 was the substrate for the subsequent late-stage functionalization and solved two synthetic problems at once. Dhp saved two reaction steps because Dyp as a starting point for the assembly of CMP 12 would require a diol protecting group during peptide coupling . Additionally, Dhp is preferred over Dyp in SPPS because of the poor nucleophilicity of the secondary amine of Dyp, resulting in poor acylation yields and long reaction times .…”

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confidence: 99%

Synthetic Marine Sponge Collagen by Late-Stage Dihydroxylation

Priem

Geyer

2017

Org. Lett.

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Based on the observation that an increased substrate size is paralleled by an enhanced diastereoselectivity, a late-stage dihydroxylation protocol toward the 21mer CMP (collagen model peptide) Ac-(Pro-Hyp-Gly)-Pro-Dyp-Gly-(Pro-Hyp-Gly)-NH is presented. C3 and C4 hydroxylation have a converse effect on the triple-helical stability of collagen. Their combined influence on the melting temperature was studied by NMR spectroscopy.

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Synthesis ofl-2,3-trans-3,4-cis-Dihydroxyproline Building Blocks for Peptide Synthesis

Cited by 24 publications

References 15 publications

Silica Morphogenesis by Alternative Processing of Silaffins in the Diatom Thalassiosira pseudonana

Silica Morphogenesis by Alternative Processing of Silaffins in the Diatom Thalassiosira pseudonana

Scaling the Amphiphilic Character and Antimicrobial Activity of Gramicidin S by Dihydroxylation or Ketal Formation

Synthetic Marine Sponge Collagen by Late-Stage Dihydroxylation

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