• Bulletin of the Korean Chemical Society
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• 제32권9호
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• pp.3425-3428
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• 2011

Apolipoprotein A-I (Apo A-I) is a major component for high density lipoproteins (HDL). A number of mimetic peptides of Apo A-I were screened from the phase-displayed random peptide library by utilizing monoclonal antibodies (A12). Mimetic peptide for A12 epitope against Apo A-I was selected as CPFARLPVEHHDVVGL (pA1). From the BLAST search, the mimetic peptide pA1 had 40% homology with Apo A-I. As a result of the structural determination of this mimotope using homo/hetero nuclear 2D-NMR techniques and NMR-based distance geometry (DG)/molecular dynamic (MD) computations, DG structure had low penalty value of 0.3-0.7 ${\AA}^2$ and the total RMSD was 0.6-1.6 ${\AA}$. The mimotope pA1 exhibited characteristic conformation including a ${\beta}$-turn from Pro[7] to His[11].

• Bulletin of the Korean Chemical Society
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• 제26권2호
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• pp.327-330
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• 2005

• Bulletin of the Korean Chemical Society
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• 제32권11호
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• pp.4016-4020
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• 2011

A number of mimetic peptides of apolipoprotein A-I, a major component for high density lipoproteins (HDL), were screened from the phase-displayed random peptide library by utilizing monoclonal antibodies (A12). A mimetic peptide for A12 epitope against apolipoprotein A-I was selected as FVLVRDTFPSSVCCP(pA2) exhibiting 45% homology with Apo A-I in the BLAST search. Solution structure determination of this mimotope was made by using 2D-NMR data and NMR-based distance geometry (DG)/molecular dynamic calculations. The resulting DG structures had low penalty value of 0.4-0.6 ${\AA}^2$ and the total RMSD of 0.7-1.7 ${\AA}$. The mimotope pA2 exhibited a characteristic ${\beta}$-turn conformation from Val[2] to Phe[8] near Pro[9] residue.

• BMB Reports
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• 제36권6호
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• pp.552-557
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• 2003

Oligomers with $\alpha$-aminooxy acids are reported to form very stable turn and helix structures, and they are supposed to be useful peptidomimetics for drug design. A recent report suggested that homochiral oxa-peptides form a strong eight-member-ring structure by a hydrogen bond between adjacent aminooxy-acid residues in a $CDCl_3$ solution. In order to design an $\alpha$-MSH analog with a stable turn conformation, we synthesized four tetramers and one pentamer, based on $\alpha$-MSH sequence, and determined the solution structures of the molecules by two-dimensional NMR spectroscopy and simulated annealing calculations. The solution conformations of the three peptidomimetic molecules (TLV, TDV, and TLL) in DMSO-$d_6$ contain a stable 7-membered-ring structure that is similar to a $\gamma$-turn in normal peptides. Newly-designed tetramer TDF and pentamer PDF have a ball-type rigid structure that is induced by strong hydrogen bonds between adjacent amide protons and carbonyl oxygens. In conclusion, the aminooxy acids, easily prepared from natural or unnatural amino acids, can be employed to prepare peptidomimetic analogues with well-defined turn structures for pharmaceutical interest.

• Molecules and Cells
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• 제25권3호
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• pp.352-357
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• 2008

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits osteoclastogenesis and is closely associated with bone resorption processes. We have designed and determined the solution structures of potent OPG analogue peptides, derived from sequences of the cysteine-rich domain of OPG. The inhibitory effects of the peptides on osteoclastogenesis are dose-dependent ($10^{-6}M-10^{-4}M$), and the activity of the linear peptide at $10^{-4}M$ is ten-fold higher than that of the cyclic OPG peptide. Both linear and cyclic peptides have a ${\beta}$-turn-like conformation and the cyclic peptide has a rigid conformation, suggesting that structural flexibility is an important factor for receptor binding. Based on structural and biochemical information about RANKL and the OPG peptides, we suggest that complex formation between the peptide and RANKL is mediated by both hydrophobic and hydrogen bonding interactions. These results provide structural insights that should aid in the design of peptidyl-mimetic inhibitors for treating metabolic bone diseases caused by abnormal osteoclast recruitment.

• 정보처리학회논문지A
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• 제16A권4호
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• pp.255-262
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• 2009

유비쿼터스 센서 네트워크(USN)에 기반한 엔터테인먼트용 자율 돌고래 로봇의 구현에 관하여 소개한다. 일반적으로 수중에서 동작하는 생체모방 로봇에 유비쿼터스 센서 네트워크와 GPS를 적용하는 것은 불가능한 일이다. 본 논문에서 제안된 엔터테인먼트용 돌고래 로봇은 수중이 아닌 수면에서 동작하므로, 사용자와의 상호작용을 중요시하며 제안된 수중 로봇의 네비게이션은 GPS정보와 배치된 USN 모트로부터 얻어진 미세한 위치 정보로부터 수행된다. 본 논문에서는 제안된 돌고래 로봇의 기계적인 구조, 센서와 엑추에이터, 마이크로컨트롤러 보드와 수영 방법, 사용자와의 상호작용의 특징을 기술한다. 엔터테인먼트 돌고래 로봇은 유저에 의한 접촉 센서의 감지 신호를 입력받아 입을 움직이거나, 꼬리를 치고, 물을 뿜어내는 등의 전형적인 응답을 보인다. 로봇의 자율성을 위하여 경로 설정, 장애물 감지 및 회피 등과 같은 로봇의 움직임뿐 아니라 인간과 로봇의 상호작용에 관련된 기능들을 마이크로컨트롤러가 제어한다. 돌고래 로봇의 위치 정보는 배치된 USN 모트의 알려진 위치 정보로부터 주기적으로 교정된다.

• Molecules and Cells
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• 제39권4호
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• pp.316-321
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• 2016

The receptor activator of nuclear factor ${\kappa}B$ (RANK) and its ligand RANKL are key regulators of osteoclastogenesis and well-recognized targets in developing treatments for bone disorders associated with excessive bone resorption, such as osteoporosis. Our previous work on the structure of the RANK-RANKL complex revealed that Loop3 of RANK, specifically the non-canonical disulfide bond at the tip, performs a crucial role in specific recognition of RANKL. It also demonstrated that peptide mimics of Loop3 were capable of interfering with the function of RANKL in osteoclastogenesis. Here, we reported the structure-based design of a smaller peptide with enhanced inhibitory efficiency. The kinetic analysis and osteoclast differentiation assay showed that in addition to the sharp turn induced by the disulfide bond, two consecutive arginine residues were also important for binding to RANKL and inhibiting osteoclastogenesis. Docking and molecular dynamics simulations proposed the binding mode of the peptide to the RANKL trimer, showing that the arginine residues provide electrostatic interactions with RANKL and contribute to stabilizing the complex. These findings provided useful information for the rational design of therapeutics for bone diseases associated with RANK/RANKL function.