An Oligomeric Ser-Pro Dipeptide Mimetic Assuming the Polyproline II Helix Conformation

Tremmel, Peter; Geyer, Armin

doi:10.1021/ja026098u

Cited by 37 publications

(23 citation statements)

References 18 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PP II is a left‐handed helical structure, characterized by (ϕ,ψ) = (−70 to −80° and 140–150°). Such structures have been detected earlier in the chemically denatured states of proteins with the presence of a positive CD band at 225 nm 52. However, the absence of a band at 225 nm for denatured dSmt3 [Fig.…”

Section: Resultssupporting

confidence: 56%

Conserved structural and dynamics features in the denatured states of drosophila SUMO, human SUMO and ubiquitin proteins: Implications to sequence‐folding paradigm

Kumar¹,

Chugh²,

Sharma³

et al. 2009

Proteins

View full text Add to dashboard Cite

We have characterized here the structural and dynamics properties of urea-denatured state of dSmt3 by multidimensional NMR at 27 degrees C and pH 5.6. The various results suggest that hydrophobic clusters as well as different native and non-native secondary structural elements are transiently formed. The backbone in the regions Gln26-Lys31 and Gly47-Gln60 shows conformationally restricted motions. The AABUF profile of the sequence reflected that this region has the highest tendency to undergo hydrophobic clustering and may thus assist the formation of transient structures. The secondary chemical shifts and coupling constants indicated that this region has strong tendency to occupy the broad beta-domain of (phi,psi) space. A number of NMR parameters indicated that the region Asp58-Gln60 (corresponding to beta3-beta4 turn in the folded state) has residual turn-like structure. The present structural and dynamics results on urea-denatured dSmt3 have been compared with the previously published results on denatured states of similar fold proteins e.g. human SUMO-1 (55% homologous), ubiquitin (13.8% homologous) and GB1. Although the sequence homology is rather poor between them, the residual structure in all cases seems to be largely native type. The implications of these to sequence-folding paradigm and initial folding processes have been discussed.

show abstract

Section: Resultssupporting

confidence: 56%

Conserved structural and dynamics features in the denatured states of drosophila SUMO, human SUMO and ubiquitin proteins: Implications to sequence‐folding paradigm

Kumar¹,

Chugh²,

Sharma³

et al. 2009

Proteins

View full text Add to dashboard Cite

show abstract

“…The synthesis of conformationally constrained β-turn mimics with native-like side chains is hampered by the expense of designing an oligocyclic scaffold that is adequately protected for solid-phase peptide synthesis (13). Polyhydroxylated dipeptides with diversified stereochemistries can be obtained from uronolactones in a straightforward way (14,15). The oxidation of the primary hydroxyl group of 2,3-isopropylidene-D-ribonolactone (1) (16) yields 2,3-isopropylidene-L-riburonolactone, which reacts with L-cysteinemethylester to thiaindolizidinone 2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Structural characterization of a β-turn mimic within a protein–protein interface

Eckhardt

Große

Essen

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

β-turns are secondary structure elements not only exposed on protein surfaces, but also frequently found to be buried in protein–protein interfaces. Protein engineering so far considered mainly the backbone-constraining properties of synthetic β-turn mimics as parts of surface-exposed loops. A β-turn mimic, Hot═Tap, that is available in gram amounts, provides two hydroxyl groups that enhance its turn-inducing properties besides being able to form side-chain-like interactions. NMR studies on cyclic hexapeptides harboring the Hot═Tap dipeptide proved its strong β-turn-inducing capability. Crystallographic analyses of the trimeric fibritin-foldon/Hot═Tap hybrid reveal at atomic resolution how Hot═Tap replaces a βI’-turn by a βII’-type structure. Furthermore, Hot═Tap adapts to the complex protein environment by participating in several direct and water-bridged interactions across the foldon trimer interface. As building blocks, β-turn mimics capable of both backbone and side-chain mimicry may simplify the design of synthetic proteins.

show abstract

“…Among the few examples we found were the tricyclic dipeptide mimetic of Reuter et al, (Fig. A,B) [Reuter et al, ], the oligomeric Ser‐Pro dipeptide mimetic of Tremmel and Geyer[Tremmel and Geyer, ], the silaproline oligomers of Martin et al (Fig. C) [Martin et al, ] and the systematic development of PPII helix‐mimetic fragments performed by Opitz et al [].…”

Section: Receptor‐bound Conformationsmentioning

confidence: 99%

Limiting Assumptions in the Design of Peptidomimetics

Marshall

Ballante

2017

Drug Development Research

View full text Add to dashboard Cite

Preclinical Research Limiting the flexibility of organic compounds to enhance their affinity and selectivity for targeting a macromolecule involved in molecular recognition has become a well-developed paradigm in medicinal chemistry. While the role of reverse-turn motifs as peptidomimetics has received the most attention, β-sheets and helices are also important motifs for protein/protein interactions. The more complicated problem of mimicking the interacting surface of noncontiguous epitopes will not be considered in this review. This limited overview focuses on efforts to use amino acid synthons as secondary-structure mimetics as well as providing examples of peptidomimetic design focused on nonpeptide synthetic chemistry in contrast. In particular, the rationale of optimal design criteria for mimicry and the many naïve violations of those criteria made in its pursuit are emphasized. Drug Dev Res 78 : 245-267, 2017. © 2017 Wiley Periodicals, Inc.

show abstract

An Oligomeric Ser-Pro Dipeptide Mimetic Assuming the Polyproline II Helix Conformation

Cited by 37 publications

References 18 publications

Conserved structural and dynamics features in the denatured states of drosophila SUMO, human SUMO and ubiquitin proteins: Implications to sequence‐folding paradigm

Conserved structural and dynamics features in the denatured states of drosophila SUMO, human SUMO and ubiquitin proteins: Implications to sequence‐folding paradigm

Structural characterization of a β-turn mimic within a protein–protein interface

Limiting Assumptions in the Design of Peptidomimetics

Contact Info

Product

Resources

About