Research Highlights

 
  1. Conjugating catalytic polyproline fragments with a self-assembling peptide produces efficient artificial hydrolases. (Published in Biomacromolecules 2020)


  2. Impacts of the terminal charged residues on polyproline conformation. Incorporating the residue with a positively charged sidechain will significantly stabilize PPII helices and disfavor PPI helices. (Published in J. Phys. Chem. B 2019)


  3. Zn(II)-His induced CMP-assemblies: morphology modulation and catalytic activity evaluation. A series of short CMPs with one or more histidine residues incorporated into the peptides were prepared and  Zn(II) was used to induce the formation of collagen assembled microstructures. By altering the location and the number of histidine residues, we found that the assembly rate was significantly affected as well as the morphology of the assembled architectures. The CMP with only one single histidine in its middle site could form pinwheel or floret-like constructs. Additionally, these CMPs also exhibited catalytic activities on ester hydrolysis in the presence of Zn(II) ions, suggesting that Zn(II)-CMP assemblies could be potentially applied to the development of artificial enzymes. (Published in Biomacromolecules 2018)


  4. Design of polyproline-based catalysts for ester hydrolysis. Using polyroline as a scaffold to design catalysts for ester hydrolysis. His , Asp, Cys, Ser, and Trp were incorporated into the i, i+3 or i-3 position of polyproline peptides to form dyads or triads for catalysis. (2S,4R)-hydroxyproline was also used to replace Pro for structure-activity study. The work demonstrates that polyproline can serve as a framework to design artificial enzymes and an robust PPII structure may increase the catalytic activity. (Published in ACS Omega 2017)


  5. Formation of AAB-type collagen heterotrimers via the C-terminal cation-π interactions. Cation-π interactions generated from Arg-Phe or Lys-Phe pair were installed into the C-terminus to serve as a nucleation force to assist the formation of AAB-type heterotrimers. Only one component of heterotrimers were found in solution. This work also suggests that the folding of such heterotrimers starts from the C-terminus. (Published in Biomacromolecules 2017


  6. Effects of glycosylation of hydroxyproline on the stability and assembly of collagen triple helices.  Glycosylation of a single hydroxyproline within a collagen-mimetic peptide destabilizes the fold of a triple helix but promote the self-assembly of collagen triple helices. (Published in Amino Acids 2016)


  7. Cation-π interaction induced folding of AAB-type collagen heterotrimers.  AAB-type collagen heterotrimer folding can be induced effectively by the interchain cation interactions between cationic and aromatic collagen-mimetic peptides. (Published in J. Phys. Chem. B 2016)


  8. Effects of the terminal aromatic residues on polyproline conformation: thermodynamic and kinetic studies. Terminal aromatic-proline interactions can increase polyproline-I structures in solution. The activation parameters of polyproline-I to polyproline-II conversion are related to the hydrophobicity of aromatic side chains. (Published in J. Phys. Chem. B 2015)

  9. Modulating the affinities of phosphopeptides for the human Pin1 WW domain using 4-substituted proline derivatives. (2S,4R)-Fluoroproline can increase the affinity of a phosphopeptide to the Pin1 WW domain by the enhancement of a C-H...π interaction. (Published in Biochemistry 2015)


  1. Folding stability modulation of the villin headpiece helical subdomain by 4-fluoro- and 4-methylphenylalanine. Two non-natural amino acids, 4-fluorophenylalanine and 4-methylphenylalanine, were used to modulate the electrostatic interactions and hydrophobic effects inside the hydrophobic core of HP36. (Published in Biopolymers 2015)

               

  1. The impact of 4-thiaproline on polyproline conformation. Although 4-thiaproline has a similar structure to that of proline and prefers an endo ring pucker, it destabilizes both polyproline-I and polyproline-II structures. On the basis of the hybrid density functional theory analysis, we demonstrate that this phenomenon could be due to the small transition barrier between an exo and an endo pucker for the thiazolidine ring of Thp in a PPI helix and a weak backbone nπ* interaction for Thp in PPII conformation. The combination of experimental and computational data allows us to gain new insights into the impact of 4-thiaproline on polyproline conformation. (Published in J. Phys. Chem. B 2014)

                   

  1. Impacts of terminal (4R)-fluoroproline (Flp) and (4S)-fluoroproline  (flp) residues on polyproline confromation. Our studies revealed that inserting 4-fluoroproline residues into the C-terminus of a polyproline peptide induces a great stereoelectronic effect on PPII stability and PPIIPPI conversion rates. From the C-terminus, a (Flp)3 triplet stabilizes PPII structure and increases the transition barrier of PPIIPPI conversion by 1.53 kJ/mol while a (flp)3 triplet destabilizes PPII  conformation and reduce the PPIIPPI transition barrier by 4.61 kJ/mol. In contrast, the 4-fluoroproline substitutions at the N-terminus do not exhibit distinct stereoelectronic effects on PPII stability and PPII→‭‬PPI conversion rates. Our data demonstrate that the C-terminal stereoelectronic effects have a more dramatic impact on PPII stability and PPIIPPI conversion kinetics. (Published in Amino Acids 2014)

   

  1. Modulating the folding stability and ligand binding affinity of Pin1 WW domain by proline ring puckering. The conserved Pro37 is a key residue involved in one hydrophobic core, plays an important role in the WW domain, and adopts a Cγ-endo ring pucker in the native structure. Pro37 was replaced with Cγ-exo biased pucker derivatives: (2S,4R)-4-hydroxyproline (Hyp), (2S,4R)-4-fluoroproline (Flp), (2S,4R)-4-methoxyproline (Mop), and C-endo biased pucker derivatives: (2S,4S)-4-hydroxyproline (hyp), (2S,4S)-4-fluoroproline (flp), (2S,4S)-4-methoxyproline (mop) to examine how a pre-organized pucker affects the folding stability and ligand-binding affinity. Only flp can stabilize the WW domain and increase its ligand affinity since both the biased endo pucker and the hydrophobic C-F group of flp have positive contributions to the protein. Together we have used 4-substituted proline derivatives and the WW domain to demonstrate that proline ring puckering can be a key factor in determining the folding stability of a protein but the choice of the derivative groups is also critical. (Published in Proteins 2014)

           
   
  1. Promoting self-assembly of collagen-related peptides into various higher-order structures by metal-histidine coordination. Two short collagen-related peptides in which histidine residues were incorporated as metal binding sites were designed and chemically synthesized: HG(PPG)9GH (X9) and HG(PPG)4(PHG)(PPG)4GH (PHG). Experimental results demonstrated the metal ion-dependent self-assembly of X9 and PHG into supramolecular structures ranging from various nano-fibrils to micro-scale spherical, laminated, and granulated assemblies. The topology and size of these higher-order structures depends both on the metal ion identity and the location of the binding sites. Most intriguingly, the assembled fibrils show similar D-periodicity to that of natural collagen. In this work, we present a metal-histidine coordination strategy to induce the self-assembly of unstable collagen-related peptides into higher-order structures. (Published in Langmuir 2012)

       

  1. Self-assembly of short collagen-related collagen peptides via cation-π interactions. Introduction of a cationic residue at the N-terminus and an aromatic residue at the C-terminus of collagen-related peptides (RG(POG)10F and RG(POG)8F) can generate favorable cation-π interactions between the termini of collagen triple helices. The experimental results indicate that such cation-π interactions can promote the self-assembly of collagen triple helices into a higher-order structure in a head-to-tail manner. Our recent work shows that cation-π interactions can serve as an effective force in preparing collagen-related biomaterials. (Published in Biochemistry 2011)

           

  1. Contributions of cation-π interactions to the collagen triple helix stability. Cation-π interactions are an important non-covalent force in proteins. Collagen is a right-handed triple helix composed of many (X-Y-Gly) repeats in the sequence. Molecular modeling indicates that cation-π interactions could be formed between the X and Y positions in adjacent collagen strands. Our studies by small peptide models show that the cation-π interactions involving Arg have a larger contribution to the conformational stability than do those involving Lys. The results also show that the formation of cation-π interactions depends on the relative positions of the cationic and aromatic residues in a strand, highlighting the unique structural features of the X and Y positions. (Published in Arch. Biochem. Biophys. 2011)

   

  1. Proline puckering to folding stability of HP36. Introduction of proline derivatives with a biased ring pucker affect the aromatic-proline interaction between Trp64 and Pro62 and the folding stability of HP36. Our study provides a valuable insight into how stereoelectronic effects interplay with aromatic-proline interactions and modulate the protein stability. (Published in Biochemistry 2010)

       

  1. Stereoelectronic effects on the transition barrier of polypropline conformational interconversion. (Published in Protein Science 2009)