A peptide is efficiently produced by reacting a carboxyl group of an amino acid or intermediate peptide in which an amino group is protected, with an alkali metal salt or alkaline earth metal salt of an amino acid in which an amino group is not protected, or of an intermediate peptide in which an N-terminal is not protected, is a two-layer solvent composed of water and a hydrophobic organic solvent.

Disclosed are an etelcalcetide intermediate and a method for synthesizing etelcalcetide. The etelcalcetide intermediate is Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The method for synthesizing the etelcalcetide includes the following steps: using N-Boc-L-Cqs-OtBu as a starting material to generate a primary product of a formula (A) by means of a substitution reaction, herein R is S-Py or Cl; and performing a coupling reaction on the primary product and Fmoc-D-Cys-OH amino acid to obtain Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The key intermediate is used for synthesizing the etelcalcetide, which may improve the purity and the yield. It is important that the raw materials for synthesizing the key intermediate are cheap and readily available, and the process is simple.

##STR00001##

Methods for making an arylomycin ring of formula t ##STR00001##
or salts or solvates thereof, wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.5, R.sup.10 and Pg.sup.1 are as defined herein.

An automated system of reactors carries out a solid-phase peptide synthesis, and more particularly a solid-phase peptide synthesizer which is automated, by means of a reactor with a liquid-recirculation loop making it possible to measure, in real time, chemical species in the reactor via measuring cells. This system includes inlet pipes, namely: pipes dedicated to the introduction of resin, pipes dedicated to the introduction of the synthesis and washing solvent, pipes dedicated to the introduction of the agent for deprotecting the amino acid introduced, pipes dedicated to the introduction of the reagents, and includes an assembly reactor and a loop for recirculation of the liquid of the reactor.

Methods of producing a peptide containing an N-substituted amino acid or N-substituted amino acid analog of the present invention include the steps of: preparing an Fmoc-protected amino acid, an Fmoc-protected amino acid analog, or an Fmoc-protected peptide; deprotecting a protecting group which have an Fmoc skeleton of the Fmoc-protected amino acid and such by using a base; and forming an amide bond by adding a new Fmoc-protected amino acid and such; and when the peptide is produced by a solid-phase method, the obtained peptide is cleaved off from the solid phase under conditions of weaker acidity than TFA. Furthermore, at least one side chain of the obtained peptide has a protecting group that is not deprotected under basic conditions and is deprotected under conditions of weaker acidity than TFA.

The present invention comprises conjugates comprising a monoclonal antibody conjugated to a cyclic PYY peptide. The invention also relates to pharmaceutical compositions and methods for use thereof. The novel conjugates are useful for preventing, treating or ameliorating diseases and disorders disclosed herein.

The embodiments disclosed herein provide a peptoid, which is a compound of Formula I or a stereoisomer, a mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. N—R.sub.4, N—R.sub.3, N—R.sub.2, and N—R.sub.1 in Formula I are

##STR00001##

respectively. The peptoid has a strong binding ability with an EpCAM protein. It can be used as molecular probes for diseases associated with an EpCAM protein, to achieve targeted therapy, in vivo imaging diagnosis and prognosis monitoring of the diseases associated with the EpCAM protein at low cost, high accuracy and high efficiency.

##STR00002##

The present disclosure relates to peptide compounds and conjugate compounds, processes, methods and uses thereof for treating cancer. For example, the compounds can comprise compounds of formula

TABLE-US-00001 X.sub.1X.sub.2X.sub.3X.sub.4X.sub.5GVX.sub.6AKAGVX.sub.7NX.sub.8FKSESY (I) (SEQ ID NO: 1) (X.sub.9).sub.nGVX.sub.10AKAGVX.sub.11NX.sub.12FKSESY (II) (SEQ ID NO: 2) YKX.sub.13LRRX.sub.14APRWDX.sub.15PLRDPALRX.sub.16X.sub.17L (III) (SEQ ID NO: 3) YKX.sub.18LRR(X.sub.19).sub.nPLRDPALRX.sub.20X.sub.21L (IV) (SEQ ID NO: 4) IKLSGGVQAKAGVINMDKSESM (V) (SEQ ID NO: 5) IKLSGGVQAKAGVINMFKSESY (VI) (SEQ ID NO: 6) IKLSGGVQAKAGVINMFKSESYK (VII) (SEQ ID NO: 7) GVQAKAGVINMFKSESY (VIII) (SEQ ID NO: 8) GVRAKAGVRNMFKSESY (IX) (SEQ ID NO: 9) GVRAKAGVRN(Nle)FKSESY (X) (SEQ ID NO: 10) YKSLRRKAPRWDAPLRDPALRQLL (XI) (SEQ ID NO: 11) YKSLRRKAPRWDAYLRDPALRQLL (XII) (SEQ ID NO: 12) YKSLRRKAPRWDAYLRDPALRPLL (XIII) (SEQ ID NO: 13) wherein X.sub.1 to X.sub.21 and n can have various different values and wherein at least one protecting group and/or at least one labelling agent is optionally connected to said peptide compound at an N- and/or C-terminal end.

The present invention provides compounds which are selective kappa-opioid receptor agonist, method of preparation of these compounds, compositions that comprise these compounds, and methods for treating kappa-opiod receptor agonist related medical disorders.

The invention relates to a peptidomimetic comprising or consisting of a D amino-acid sequence having at least 75% identity with SEQ ID NO: 1 or SEQ ID NO: 2, or variants or fragments thereof, in particular a peptidomimetic having the capability to interact at least with: neutrophils and/or neutrophil granules, and/or lactoferrin, and/or globet-cells and/or Muc2 proteins, and/or mucus and/or airway sputum. The peptidomimetic may have the capacity to adopt a multimeric, especially a trimeric, organization, and can be labelled, or associated with a reporter or a carrier entity, or associated with an active molecule. The invention also relates to a Solid-Phase Synthesis method for synthesizing a peptidomimetic of the invention, compositions comprising the same and use of the peptidomimetics as a medicamentor an inflammation marker or a neutrophilic inflammation marker. The invention also relates to the use of a peptidomimetic as a probe or marker for staining purposes, or to detect mucus production, or neutrophils, or to detect or monitor diseases or conditions, especially neutrophilic inflammation. The invention also relates to the use of a polypeptide comprising or consisting of SEQ ID NO: 3, or variants or fragments thereof, as probe or marker for staining lactoferrin, in particular neutrophil lactoferrin, or a probe or marker for investigating neutrophilic inflammation, especially in an imaging method.