Pseudoproline

Note The oxazolidine-4-carboxylic acids as precursors of serine and threonine residues are also named pseudoprolines, i.e. Ser(TrPro) and Thr(WPro), 139169 whereby oxazolidine-4-carboxylic acids with substituents at C2 are designed as Ser(WR R Pro) and Thr( PR R Pro), respectively.]... 

Note 4-Thiaproline is also named as pseudoproline, Cys(WPro), 169 whereby the related disubstituted derivatives at the C5 position of the proline ring are defined as... 

Scheme 14 Serine (Oxa), Threonine [Oxa(5-Me)], and Cysteine (Thz) Derived Pseudoprolines[82 851...

Due to the preference for a cis-amide bond[93] with the preceding residue of C2-substituted pseudoprolines, their incorporation results in a kink conformation of the peptide backbone, thus preventing peptide aggregation, self-association, or (3-structure formation. 

Scheme 15 Strategies for the Use of Pseudoproline in Solid-Phase Peptide Synthesis182-85 ...

Peptide Synthesis and Introduction of Pseudoproline Building Blocks 1831... 

Fig. 1.2.4. Bulky substituents attached to the heterocyclic scaffold make 5-tert-butylproline (a) and pseudoprolines (X = O or S) (b) efficient syn-proline mimics, (c) Imide isomerism N-terminal to pipecolyl residues.

SCHEME 11.5 Efficient concept for convergent method using the pseudoproline scaffold reported by (a) Unverzagt et al. and (b) Danishefsky et al. BMP, butyl-3-mercaptopropionate DIC, diisopropylcarbodiimide DMF, /V,/V-di methyl form amide Gly, glycine HATU,... 

Studies on host-guest peptides have shown that incorporation of a proline residue into peptides which have a high tendency to fold into ordered secondary structures disrupts the onset of helical as well as P-sheet conformations and increases solubility and coupling rates.f Based on this observation, serine- and threonine-derived oxazolidine, and cysteine-derived thiazolidine derivatives (pseudoprolines) were proposed as valuable tools for combining protection of their side-chain functions with the simultaneous solubilization of the peptide chain. Due to the induction of kink conformations in the peptide backbone, originating from the preference of these pseudoproline residues to adopt the cis-imide bond configuration, insertion of such derivatives into peptides prevents self-association and P-structure formation. 

Scheme 5 Synthesis of Pseudoproline Dipeptides as Building Blocks for Peptide Synthesis Utilizing Fmoc/ tBu Chemistryl 1...

Mutter and co-workers have defined oxa- and thiaproline derivatives of serine, threonine, and cysteine with Ser( PPro), Thr( PPro), and Cys-( Pro), respectively, where the abbreviation PPro indicates the relationship to proline (with heteroatomic ring substitution in position 4). Pseudoprolines with substitution in position 2 of the proline ring are named Ser/Thr/Cys( Pro). 

The protecting groups of hydroxy moieties can be classified into three different types, namely alkyl ethers, carbonic acid esters, and sUyl ethers (Scheme 1). Pseudoprolines derived from serine and threonine have also been suggested as a form of temporary protection for both of these amino acids. 

Pseudoprolines (Synthesis of Dipeptide Building Units from Serine and Threonine)... 

Reconversion of Pseudoproline Moieties into Hydroxy Amino Acid DerivativestO l... 

However, it can be difficult to couple to the hindered Hmb-protected amino acids so in cases where the peptide chain contains Ser or Thr, oxazolidine dipeptide derivatives 3 have been employed (Scheme 7). These pseudoproline derivatives induce a turn in the peptide chain disrupting P-sheet formation. 

Like morphiceptin and PL017, cisltrans isomerization occurs around the Tyr-Pro amide bond in endomorphin-1, with similar populations (75%trans, 25%cis) found for the two conformations (819). Based on structural comparison of the cis and trans conformations of endomorphin-1 to other /x- and 8-selective opioid peptides, Podlogar et al. proposed that the trans conformation was the bioactive form (819). Recently, Schiller and coworkers reported endomorphin-2 and morphiceptin analogs containing a pseudoproline derivative in... 

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